Mortality In Schizophrenia Research Articles

Risk Factors for Natural Cause Mortality in Schizophrenia

Schizophrenia is associated with premature mortality from mostly natural causes. Decreased cognitive functioning has been identified as a determinant of mortality in the general population. However, there have been few prospective studies of this issue in persons with schizophrenia. To examine whether lower cognitive functioning is a risk factor for natural cause mortality in schizophrenia. This prospective cohort study included persons with schizophrenia or schizoaffective disorder enrolled between February 1, 1999, and December 31, 2022, at a nonprofit psychiatric system in Baltimore, Maryland. Participants were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and other clinical measures. Natural cause mortality. Associations of cognitive function, obesity, tobacco smoking, and medical conditions with natural cause mortality were evaluated using Cox proportional hazards regression models. Of the 844 participants enrolled (mean [SD] age, 39.6 [12.1] years; 533 male [63.2%]), 158 (18.7%) died of natural causes during a median follow-up of 14.4 years (range, 7.0 days to 23.9 years). The most significant factor associated with mortality was lower cognitive functioning as measured by the RBANS (Cox coefficient, -0.04; 95% CI, -0.05 to -0.03; z = -5.72; adjusted P < .001). Additional factors independently associated with mortality included the diagnosis of an autoimmune disorder (hazard ratio [HR], 2.86; 95% CI, 1.83-4.47; z = 4.62; adjusted P < .001), tobacco smoking (HR, 2.26; 95% CI, 1.55-3.30; z = 4.23; adjusted P < .001), diagnosis of chronic obstructive pulmonary disease (HR, 3.31; 95% CI, 1.69-6.49; z = 3.48; adjusted P = .006), body mass index as a continuous variable (HR, 1.06; 95% CI, 1.02-1.09; z = 3.30; adjusted P = .01), diagnosis of a cardiac rhythm disorder (HR, 2.56; 95% CI, 1.40-4.69; z = 3.06; adjusted P = .02), and being divorced or separated (HR, 1.80; 95% CI, 1.22-2.65; z = 2.97; adjusted P = .02). An RBANS score below the 50th percentile displayed a joint association with being a smoker, having an elevated body mass index, and having a diagnosis of an autoimmune or a cardiac rhythm disorder. In this prospective cohort study, lower cognitive functioning was a risk factor for natural cause mortality in schizophrenia. Efforts should be directed at methods to improve cognitive functioning, particularly among individuals with additional risk factors.

Effects of antipsychotic treatment on cardio-cerebrovascular related mortality in schizophrenia: A subanalysis of a systematic review and meta-analysis with meta-regression of moderators

To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia. We found first generation antipsychotics (FGA) to be associated with higher mortality in incident samples of schizophrenia (oral FGA [RR=2.20, 95 %CI=1.29–3.77, k = 1] and any FGA [RR=1.70, 95 %CI=1.20–2.41, k = 1]). Conversely, second generation antipsychotics (SGAs) and clozapine were associated with reduced cardio-cerebrovascular-related mortality, in prevalent samples of schizophrenia. Subgroup analyses with NOS score ≥7 (higher quality) demonstrated a significantly increased cardio-cerebrovascular disorder-related mortality, among those exposed to FGAs vs SGAs. Meta-regression analyses demonstrated a larger association between antipsychotics and decreased risk of mortality with longer follow-up, recent study year, and higher number of adjustment variables. Overall, this subanalysis of a systematic review contributes to the evolving understanding of the complex role of antipsychotic treatment for cardio-cerebrovascular mortality in schizophrenia, paving the way for more targeted interventions and improved patient outcomes.

Lipid-modifying agents and risk of all-cause, natural and suicide mortality in schizophrenia: nationwide cohort study.

Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied. This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia. This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent. This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association. Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population.

Incidence, prevalence, and mortality of schizophrenia from 2016 to 2020 in Shandong, China

The epidemiology of schizophrenia has been reported in many countries. However, due to the limitations of those studies, the findings cannot be generalized to other parts of the world, especially in China. In this study, the incidence, prevalence, and mortality of schizophrenia in Shandong, China were calculated using data from the National Severe Mental Disorder Registration System collected between 2016 and 2020 and census data from 2010 to 2020. The overall incidence decreased from 9.61 per 100,000 in 2016 to 4.40 per 100,000 in 2020, the aggregate prevalence was approximately 3.20 per 1000, and the overall mortality ranged from 6.17 per 100,000 to 7.71 per 100,000. The evidence from this study indicated that the incidence, prevalence, and mortality of schizophrenia were higher in rural areas than in urban areas. Females had higher incidence, prevalence, and mortality than males. This study provided epidemiological information on schizophrenia and opened avenues for future research.

Epidemiology of depression in schizophrenia patients living in Africa: a systematic review and meta-analysis

IntroductionVarious comorbid conditions can worsen the morbidity and mortality of schizophrenia, and this is the case for depression, especially through suicidal behaviors and cardiometabolic impairments. There is a scarcity of summarizing data on depressive symptoms and disorders among schizophrenia patients living in Africa.ObjectivesThe aim of this meta-analytic review was to estimate the prevalence of depression in people living with schizophrenia in Africa.MethodsWe systematically searched for relevant articles published from inception to July 05, 2022, in PubMed/MEDLINE, EMBASE, and African Journals Online. We appraised the risk of bias using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for studies reporting prevalence data, and estimated the pooled prevalence of depression among patients with schizophrenia using a random-effects meta-analytic model. We performed meta-regression and subgroup analyses to assess potential mediators of our estimates. We based the report of our findings on the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (2020). We registered our protocol in PROSPERO (CRD42022315717).ResultsFrom 791 initial records, 10 studies were finally included in our qualitative and quantitative syntheses (Figure 1). These studies encompassed 2265 patients with schizophrenia (male-to-female ratio = 1.94), and were conducted between 2001 and 2019, in Egypt (n = 1/10), Ethiopia (n = 4/10), Morocco (n = 1/10), Nigeria (n = 1/10), South Africa (n = 2/10), and Tunisia (n = 1/10). The mean age of participants ranged from 33.8 to 49.2 years, and the most used tool was the Calgary Depression Scale for Schizophrenia (n = 4/10). The pooled prevalence rate of depression was 23.93% (95% CI: 19.43% – 28.73%), with substantial heterogeneity (I² = 84%). The prevalence of depression significantly varied according to screening tool used. The frequencies for Northern and Sub-Saharan Africa were respectively 31.9% (95% CI: 24.8% – 39.5%) and 21.1% (95% CI: 16.7% – 25.9%), with a significant difference between these subgroups (Figure 2). A higher prevalence of depression was associated with a lower percentage of schizophrenia patients with high education levels. Among schizophrenia people with depression (n = 250), 46.04% (95% CI: 30.07% – 62.42%) reported past or current suicide behaviors. The risk of bias was low for three studies, moderate for two studies, and high for five studies. The certainty was very low, and we found no publication bias.Image:Image 2:ConclusionsApproximately one in every four schizophrenia patients living in Africa was positively screened for depression. This review draws health professionals’ attention caring people with schizophrenia, and calls for further studies with a harmonization of screening tool, a better representativity of some subregions, and the assessment of key potential factors such as perceived stigma and self-stigma.Disclosure of InterestNone Declared

A Systematic Review on the Potential of Aspirin to Reduce Cardiovascular Risk in Schizophrenia.

Cardiovascular disease (CVD), including heart disease and stroke, continues to be the leading cause of death worldwide. Patients with mental health disorders, including schizophrenia (SCZ) are known to have an increased risk for CVD. Given the association with metabolic syndrome, patients with SCZ are often prescribed metformin and statins but its impact remains unsatisfactory. The use of aspirin (ASA) to decrease cardiovascular risk in the general population has been thoroughly investigated and clear guidelines are currently in place. Since adjuvant treatment with ASA could possibly decrease CVD risk and mortality in SCZ, we conducted a systematic review of the literature to determine the state of the current literature on this subject. Our systematic review points to gaps in the literature on CVD prevention in SCZ and illustrates an obvious need for further research. Although several studies have shown increased CVD risk in SCZ, to date, no research has been conducted on the utilization of CVD preventative treatment such as ASA for SCZ.

Mortality in Schizophrenia-Spectrum Disorders: Recent Advances in Understanding and Management.

Schizophrenia is a life-shortening disease and life expectancy in patients may be 15-20 years shorter than in the general population, with increasing longevity gap over time. Premature mortality in schizophrenia-spectrum disorders is mainly due to preventable natural causes, such as cardio-vascular disease, infections, respiratory tract diseases and cancer, alongside suicide, homicide and accidents. There is a complex interplay of factors that act synergistically and cause physical morbidity to patients and subsequent mortality. Smoking, alcohol/substance abuse and sedentary life style, alongside disease-related factors, such as metabolic abnormalities and accelerating aging contribute to physical morbidity. Moreover, the symptomatology of psychosis and stigma may limit patients' access to quality medical care. Interventions to promote physical health in those patients should be multifaceted, and should target all patient-related modifiable factors, but also should address service-related healthcare disparities. Long-term antipsychotic use (including clozapine and long-acting injectables) is associated with substantially decreased all-cause mortality, including suicide and cardiovascular mortality, in patients with schizophrenia despite the well-known cardiometabolic adverse effects of second-generation agents. Integrated care may involve co-location of physical and mental health services, liaison services, shared protocols and information sharing systems, and has emerged as a way to address the physical health needs of those patients. Interventions to address mortality in schizophrenia and related syndromes should take place as early as possible in the course of the patients' treatment, and could be an integral component of care delivered by specialized early intervention services.

Exposure to psychotropic medications and mortality in schizophrenia: a 5-year national cohort study.

Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia. We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted. A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07-1.27; HR in moderate dose: 1.32, 95% CI 1.21-1.44; HR in high dose: 1.83, 95% CI 1.67-2.01)]. The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study.

The Cumulative Effect of Antipsychotic Usage on Mortality in Schizophrenia: A Nationwide Population-based Cohort Study in Korea.

ObjectiveTo investigate the cumulative effect of antipsychotics at different dosages on mortality in patients with schizo-phrenia.MethodsWe analyzed data from the Korean National Health Insurance System−National Sample Cohort covering the 2002−2013 period. We used Cox regression analysis to calculate hazard ratios for mortality risks according to cumulative antipsychotic exposure levels (low, moderate, and high).ResultsOur analyses revealed no significant association between antipsychotic exposure and mortality (either all-cause or cause-specific) in patients with schizophrenia.ConclusionOur results imply that the excess mortality of patients with schizophrenia is attributable to factors other than antipsychotic usage.

Elevated risk of liver steatosis in first-episode psychosis patients: Results from a 3-year prospective study

BackgroundCardiometabolic disorders are largely responsible for excess mortality in schizophrenia. Non-alcoholic fatty liver disease (NAFLD) is increasingly relevant in the development of metabolic risk factors that have been associated with antipsychotic treatment.We aimed to assess the incidence of NAFLD and metabolic disturbances during the first 3 years of antipsychotic treatment in patients with first episode of psychosis (FEP), and compare it with the incidence in a control group. MethodsData were obtained from patients with psychosis (n = 160) and healthy controls (n = 66) included in the Cantabria's clinical and research program on FEP (PAFIP) from 2012 to 2018. Fatty Liver Index (FLI) was used to estimate the amount of fat in the liver. FLI has been validated for the diagnosis of NAFLD against different standards such as liver ultrasound and biopsy. FLI and metabolic parameters were registered at baseline, 3 months and then yearly for 3 years. ResultsAt the end of the follow-up (3-years), 21.9 % of patients with psychosis developed a FLI ≥ 60, suggestive of liver steatosis, compared to only a 3 % of subjects within the control group (X2 = 12.120; p < 0.001). In the FEP patients group, developing a FLI ≥ 60 was statistically associated with significant increments in metabolic parameters, and with Metabolic Syndrome (MetS) (X2 = 16.151; p < 0.001) and high blood pressure (X2 = 10.654; p = 0.001). ConclusionsHaving a first episode of non-affective psychosis was significantly associated with developing liver steatosis (FLI ≥ 60) in the first three years after initiating antipsychotic treatment. The results highlight the importance of early screening the emergence of NAFLD in schizophrenia patients.

Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors.

People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random-effects meta-analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all-cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific-cause mortality. Publication bias, subgroup and meta-regression analyses, and quality assessment (Newcastle-Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all-cause mortality was increased in people with schizophrenia versus any non-schizophrenia control group (RR=2.52, 95% CI: 2.38-2.68, n=79), with the largest risk in first-episode (RR=7.43, 95% CI: 4.02-13.75, n=2) and incident (i.e., earlier-phase) schizophrenia (RR=3.52, 95% CI: 3.09-4.00, n=7) versus the general population. Specific-cause mortality was highest for suicide or injury-poisoning or undetermined non-natural cause (RR=9.76-8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79-7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio-cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All-cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001-0.02, p=0.02). Individuals with schizophrenia <40 years of age had increased all-cause and suicide-related mortality compared to those ≥40 years old, and a higher percentage of females increased suicide-related mortality risk in incident schizophrenia samples. All-cause mortality was higher in incident than prevalent schizophrenia (RR=3.52 vs. 2.86, p=0.009). Comorbid substance use disorder increased all-cause mortality (RR=1.62, 95% CI: 1.47-1.80, n=3). Antipsychotics were protective against all-cause mortality versus no antipsychotic use (RR=0.71, 95% CI: 0.59-0.84, n=11), with largest effects for second-generation long-acting injectable anti-psychotics (SGA-LAIs) (RR=0.39, 95% CI: 0.27-0.56, n=3), clozapine (RR=0.43, 95% CI: 0.34-0.55, n=3), any LAI (RR=0.47, 95% CI: 0.39-0.58, n=2), and any SGA (RR=0.53, 95% CI: 0.44-0.63, n=4). Antipsychotics were also protective against natural cause-related mortality, yet first-generation antipsychotics (FGAs) were associated with increased mortality due to suicide and natural cause in incident schizophrenia. Higher study quality and number of variables used to adjust the analyses moderated larger natural-cause mortality risk, and more recent study year moderated larger protective effects of antipsychotics. These results indicate that the excess mortality in schizophrenia is associated with several modifiable factors. Targeting comorbid substance abuse, long-term maintenance antipsychotic treatment and appropriate/earlier use of SGA-LAIs and clozapine could reduce this mortality gap.

Associations of common genetic risk variants of the muscarinic acetylcholine receptor M2 with cardiac autonomic dysfunction in patients with schizophrenia

Objectives Decreased vagal modulation, which has consistently been observed in schizophrenic patients, might contribute to increased cardiac mortality in schizophrenia. Previously, associations between CHRM2 (Cholinergic Receptor Muscarinic 2) and cardiac autonomic features have been reported. Here, we tested for possible associations between these polymorphisms and heart rate variability in patients with schizophrenia. Methods A total of three single nucleotide polymorphisms (SNPs) in CHRM2 (rs73158705 A>G, rs8191992 T>A and rs2350782 T>C) that achieved significance (p < 5 * 10−8) in genome-wide association studies for cardiac autonomic features were genotyped in 88 drug-naïve patients, 61 patients receiving antipsychotic medication and 144 healthy controls. Genotypes were analysed for associations with parameters of heart rate variability and complexity, in each diagnostic group. Results We observed a significantly altered heart rate variability in unmedicated patients with identified genetic risk status in rs73158705 A>G, rs8191992 T>A and rs2350782 T>C as compared to genotype non-risk status. In patients receiving antipsychotic medication and healthy controls, these associations were not observed. Discussion We report novel candidate genetic associations with cardiac autonomic dysfunction in schizophrenia, but larger cohorts are required for replication.

Educational attainment and mortality in schizophrenia.

BackgroundIndividuals suffering from schizophrenia have a reduced life expectancy with cardiovascular disease (CVD) as a major contributor. Low educational attainment is associated with schizophrenia, as well as with all‐cause and CVD mortality. However, it is unknown to what extent low educational attainment can explain the increased mortality in individuals with schizophrenia.AimHere, we quantify associations between educational attainment and all‐cause and CVD mortality in individuals with schizophrenia, and compare them with the corresponding associations in the general population.MethodAll Norwegian citizens born between January 1, 1925, and December 31, 1959, were followed up from January 1, 1990, to December 31, 2014. The total sample included 1,852,113 individuals, of which 6548 were registered with schizophrenia. We estimated hazard ratios (HR) for all‐cause and CVD mortality with Cox models, in addition to life years lost. Educational attainment for index persons and their parents were included in the models.ResultsIn the general population individuals with low educational attainment had higher risk of all‐cause (HR: 1.48 [95% CI: 1.47–1.49]) and CVD (HR: 1.59 [95% CI: 1.57–1.61]) mortality. In individuals with schizophrenia these estimates were substantially lower (all‐cause: HR: 1.13 [95% CI: 1.05–1.21] and CVD: HR: 1.12 [95% CI: 0.98–1.27]). Low educational attainment accounted for 3.28 (3.21–3.35) life years lost in males and 2.48 (2.42–2.55) years in females in the general population, but was not significantly associated with life years lost in individuals with schizophrenia. Results were similar for parental educational attainment.ConclusionsOur results indicate that while individuals with schizophrenia in general have lower educational attainment and higher mortality rates compared with the general population, the association between educational attainment and mortality is smaller in schizophrenia subjects than in the general population.

Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence.

Tobacco use is the top preventable cause of early mortality in schizophrenia. Over 60% of people with schizophrenia smoke, three times the general prevalence. The biological basis of this increased risk is not understood, and existing interventions do not target schizophrenia-specific pathology. We therefore used a connectome-wide analysis to identify schizophrenia-specific circuits of nicotine addiction. We reanalyzed data from two studies: In Cohort 1, 35 smokers (18 schizophrenia, 17 control) underwent resting-state fMRI and clinical characterization. A multivariate pattern analysis of whole-connectome data was used to identify the strongest links between cigarette use and functional connectivity. In Cohort 2, 12 schizophrenia participants and 12 controls were enrolled in a randomized, controlled crossover study of nicotine patch with resting-state fMRI. We correlated change in network functional connectivity with nicotine dose. In Cohort 1, the strongest (p < 0.001) correlate between connectivity and cigarette use was driven by individual variation in default mode network (DMN) topography. In individuals with greater daily cigarette consumption, we observed a pathological expansion of the DMN territory into the identified parieto-occipital region, while in individuals with lower daily cigarette consumption, this region was external to the DMN. This effect was entirely driven by schizophrenia participants. Given the relationship between DMN topography and nicotine use we observed in Cohort 1, we sought to directly test the impact of nicotine on this network using an independent second cohort. In Cohort 2, nicotine reduced DMN connectivity in a dose-dependent manner (R = −0.50; 95% CI −0.75 to −0.12, p < 0.05). In the placebo condition, schizophrenia subjects had hyperconnectivity compared to controls (p < 0.05). Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.

Long-term effects of antipsychotics on mortality in patients with schizophrenia: a systematic review and meta-analysis.

To gather current evidence on the impact of antipsychotics on long-term mortality in patients with schizophrenia. We systematically searched for articles in Embase, PubMed, and PsycINFO reporting the long-term mortality (follow-up > 1 year) of patients with schizophrenia who were using any antipsychotics. We then conducted multiple meta-analyses to determine differences in long-term mortality between different types of antipsychotics. We identified 45 articles that provided unadjusted long-term mortality rates, including 46,171 deaths during 2,394,911 person-years. The pooled mortality rate was 9.9 (95%CI = 7.4-12.7) per 1,000 person-years. The unadjusted crude mortality rate of antipsychotic drug users was lower than that of non-users (risk ratio [RR] = 0.546, 95%CI = 0.480-0.621), first-generation antipsychotics caused higher all-cause mortality than second-generation antipsychotics (RR = 1.485, 95%CI = 1.361-1.620), and polypharmacy had better effects than monotherapy on long-term mortality (RR = 0.796, 95%CI = 0.689-0.921). As for the causes of death, heart disease and cardiovascular disease ranked highest among cause-specific mortality (5.6 per 1,000 person-years). Since antipsychotics had a beneficial effect on long-term mortality in schizophrenia, greater precaution should be taken with patients who do not take them. However, since disease severity, comorbidities, and other confounding factors cannot be fully controlled, further research and verification are needed.

METABOLIC EFFECTS OF ANTIPSYCHOTIC TREATMENT IN SCHIZOPHRENIA

BACKGROUND: It is well established that morbidity and mortality of Schizophrenia is signicantly increased due to the metabolic derangements caused by anti-psychotic medications which in turn are potent cardiovascular risk factors. Despite this widespread knowledge of metabolic risks of antipsychotic treatment, the metabolic parameters of the patients are rarely taken into consideration while prescribing antipsychotic medications in India. AIM:To determine the effects of antipsychotic treatment on the metabolic parameters in drug naïve patients of schizophrenia. METHOD: Eighty consecutive drug naive schizophrenia patients were assessed for 05 metabolic parameters which form the criteria of metabolic syndrome (NCEP- ATPIII). These parameters were again assessed after 06 months of treatment in the same set of patients. The data was then analyzed for changes in metabolic parameters in context of treatment with rst and second generation antipsychotics. RESULT: Our study found that there were signicant changes in the metabolic parameters after 06 months of treatment with anti-psychotic medications. CONCLUSION:Antipsychotic medications, both rst and second generation, cause signicant derangements in the metabolic parameters. Thus, metabolic parameters should always be taken into consideration before starting of antipsychotic treatment as well as during follow up.

Diabetes complication burden and patterns and risk of mortality in people with schizophrenia and diabetes: A population-based cohort study with 16-year follow-up

Schizophrenia is associated with increased prevalence of diabetes. However, risk of diabetes complications as well as the impact of complication burden and patterns on subsequent mortality risk in schizophrenia patients with co-existing diabetes is understudied. This population-based, propensity-score matched (1:10) cohort study identified 6991 patients with incident diabetes and pre-existing schizophrenia and 68,682 patients with incident diabetes only (comparison group) between 2001 and 2016 in Hong Kong, using territory-wide medical-record database of public healthcare services. Complications were measured by Diabetes Complications Severity Index (DCSI), which stratified complication burden into 6 levels (DCSI score=0, 1, 2, 3, 4, or ≥5). Associations of diabetes complications, in terms of DCSI scores (complication burden), specific types and two-way combinations of complications (complication patterns), with all-cause mortality rate in schizophrenia were evaluated using Cox proportional-hazards models. Schizophrenia group had comparable macrovascular (adjusted OR 0.99 [95% CI 0.92–1.06]) and lower microvascular (0.79 [0.73–0.86]) complication rates relative to comparison group. Mortality risk ratio for schizophrenia was elevated at all complication burden levels, which conferred incremental impact on excess mortality in both groups. Cardiovascular diseases (1.60 [1.45–1.77]) and cerebrovascular-metabolic diseases (2.74 [1.25–5.99]) were associated with the highest differential mortality in schizophrenia among various specific complications and complication combinations, respectively. Our results indicate that schizophrenia patients with co-existing diabetes are at increased risk of excess mortality relative to those with diabetes alone, regardless of complication burden levels. Implementation of multilevel, targeted interventions is needed to improve diabetes-related outcomes and reduce mortality gap in this vulnerable population.

785Excess mortality in severe mental disorders: a systematic review and meta-regression

Abstract Background Decades worth of epidemiological studies, synthesised by systematic reviews and meta-analyses, have consistently shown that people with severe mental disorders (SMD) have a higher risk of mortality compared to the general population, which has not improved over time. One of the major limitations of previous reviews is the use of meta-analytic models to synthesise mortality estimates without taking into account potential sources of heterogeneity. Methods A systematic review of studies examining mortality in people with schizophrenia and bipolar disorder compared to the general population was conducted. Estimates of all-cause and cause-specific mortality were calculated using meta-regression models to quantify and adjust for the effects of covariates, including both study-level and population-level factors. Results A total of 76 studies were included in the analyses. The adjusted relative risk for all-cause mortality in schizophrenia was 2.80 (95% CI 2.30 to 3.41) and 2.33 (95%CI 2.01 to 2.71) for bipolar disorder. Mortality was elevated in each cause of death examined, across both unnatural and natural causes. Some heterogeneity was explained by age and sex. Conclusions The mortality gap for people with SMD compared to the general population remains unchanged. Most of the heterogeneity between studies could not be accounted for by the covariates included in our analyses. Key messages More work needs to be done towards understanding the causal factors underlying excess mortality in people with SMD in order to achieve more equitable health outcomes.

Subsequent Dyslipidemia and Factors Associated with Mortality in Schizophrenia: A Population-Based Study in Taiwan.

Background: Persons with schizophrenia are at greater risk of developing subsequent medical conditions. To date, few studies have examined comprehensively the risks, mortality and survival rates in schizophrenia and subsequent dyslipidemia over different time periods. The objective of this study was to evaluate the occurrence of subsequent dyslipidemia after the diagnosis of schizophrenia, and factors associated with mortality and survival rate in patients with schizophrenia. Methods: We used a population-based cohort from Taiwan National Health Insurance Research Database, to investigate in patients whom were first diagnosed with schizophrenia during the period from 1997 through 2009, the risk of subsequent dyslipidemia during follow-up. Cumulative incidences and hazard ratios after adjusting for competing mortality risks were calculated. Results: A total of 20,964 eligible patients were included. Risks (i.e., comorbidity) and protective factors (i.e., statin use) have significant impacts on mortality. The mortality exhibits a U-shaped pattern by age. After 50, the risk of death increases with age. Risk of mortality before 50 increases with a decrease in age. Risks differed by the duration time to subsequent dyslipidemia after schizophrenia. Mean duration was 63.55 months in the survive group, and 43.19 months in the deceased group. The 5-, 10-, and 15-year survival rates for patients with schizophrenia and subsequent dyslipidemia were 97.5, 90, and 79.18%, respectively. Conclusion: Early occurrence of subsequent dyslipidemia is associated with increased overall mortality in patients with schizophrenia.

Morbidity and mortality in schizophrenia with comorbid substance use disorders in Finland and Sweden

IntroductionSchizophrenia is highly comorbid with substance use disorders (SUD) but large epidemiological cohorts exploring the prevalence and prognostic significance of SUD are lacking.ObjectivesTo investigate the prevalence of SUD in patients with schizophrenia in Finland and Sweden, and the effect of these co-occurring disorders on risks of psychiatric hospitalization and mortality.Methods45,476 individuals with schizophrenia from two independent national cohort studies, aged &lt;46 years at cohort entry, were followed during 22 (1996-2017, Finland) and 11 years (2006-2016, Sweden). We first assessed SUD prevalence (excluding smoking). Then we performed Cox regression on risk of psychiatric hospitalization and mortality in patients with schizohrenia and SUD compared with those without SUD.ResultsThe prevalence of SUD in specialized healthcare ranged from 26% (Finland) to 31% (Sweden). Multiple drug use and alcohol use disorders were the most prevalent SUD, followed by cannabis use disorders. Any SUD comorbidity, and particularly multiple drug use and alcohol use, were associated with 50% to 100% increases in hospitalization and mortality compared to individuals without SUD. Elevated mortality risks were observed especially for deaths due to suicide and other external causes. All results were similar across countries.ConclusionsCo-occurring SUD, and particularly alcohol and multiple drug use, are associated with high rates of hospitalization and mortality in patients with schizophrenia. Preventive interventions should prioritize detection and tailored treatments for these co-morbidities, which often remain underdiagnosed and untreated.Conflict of interestML: Genomi Solutions Ltd, Nursie Health Ltd, Sunovion, Orion Pharma, Janssen-Cilag, Finnish Medical Foundation, Emil Aaltonen Foundation. HT, EMR, AT: Eli Lilly, Janssen–Cilag. JT: Eli Lilly, Janssen-Cilag, Lundbeck, Otsuka.