Mortality rates in psychiatric hospitals reflect the intricate challenges faced within mental healthcare systems globally. Mortality auditing of in-patient psychiatric hospitals for a period extending 14 years is rare in low-income countries. We are reporting a 15-year mortality review of Sudan's National Psychiatric Hospitals. It is intended to enhance the standard of care in low-resource settings.

A retrospective audit was conducted in primary psychiatric hospitals across Sudan's capital city over a 15-year period. Missing or incomplete data were addressed by cross-referencing available hospital records, consulting medical staff for clarifications when possible, and excluding cases where critical information was unavailable. Data on deceased patients were collected from hospital records, encompassing demographic details, medical histories, psychiatric diagnoses, pharmacological interventions, and causes of death.

The study identified 108 deaths out of 28,085 admissions, yielding a mortality rate of 0.38 per cent. The majority of deceased patients were male 71 (65.7%), aged below 40 years 65 (60.2%), and experienced shorter durations of hospital stay before death, with significant mortality occurring within the first week of admission. Common causes of death included infections 30 (27.7%), circulatory failure 27 (24.3%), and no clear cause 17 (15.7%). The main diagnoses of deceased patients were, major mood disorders and mania 42 (38.9%), schizophrenia /schizophrenia-like psychosis 27 (25.0%) and organic psychosis and drug-induced psychosis 16 (14.8%). Haloperidol emerged as the most frequently prescribed medication before death.

Infection and circulatory failure are the leading causes of mortality in Sudanese mental hospitals, necessitating a thorough examination to find remedies for these avoidable problems. Additionally, enhanced monitoring and early intervention, particularly in the critical initial phase of hospitalization, are essential for mitigating mortality risks associated with psychotropic medications.

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.

Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE.

This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences.

Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05).

PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.

Venous thromboembolism (VTE) poses a significant threat to individuals' health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE.

We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings.

A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 μg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05).

Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.

Schizophrenia is associated with early mortality of 15 to 20 years, and 80 % of deaths are due to cardiovascular disease with a three-times greater risk of sudden-cardiac-death. While lifestyle, medications, genetics, and healthcare disparities are contributing factors, the etiology of this complex process is not fully understood. The aim of this study is to examine cardiac-related healthcare utilization and electrocardiogram (ECG) outcomes in schizophrenia at the end of life (EOL). A cohort of individuals with schizophrenia (SG) (n = 610, ≥50 years) were identified retrospectively from a unified clinical data platform and measures of cardiovascular healthcare utilization were evaluated within a 12-month period prior to death. Similarly, a control group (n = 610) was randomly identified and matched by gender (53 % females) and age of death (72.8 ± 12.4 years). Statistical methods included Cochran-Mantel-Haenszel and mixed-effects logistic & linear regression tests with adjustments for match strata and marital status, race, age, and gender as covariates. Results indicate that SG was more likely to be unmarried, unemployed, or from minority groups (all p < 0.001), and more likely to have diabetes and/or cardiovascular disease (p < 0.001). SG was less likely to receive an ECG (p = 0.001) or cardiac catheterization procedure (p < 0.001). SG had a greater mean QTc (447.2 ms vs. 434.6 ms; p = 0.001) and were twice as likely to have "prolonged QT" on ECG report (p = 0.006). In conclusion, SG had reduced likelihood of cardiac-related healthcare interventions, and despite greater likelihood of prolonged QTc, a recognized biomarker of cardiac risk, ECG was less likely at EOL. Given greater cardiac comorbidity and risk of sudden cardiac death in schizophrenia, improved practice guidelines are needed.

Severe mental illnesses (SMI), such as schizophrenia and bipolar disorder, are associated with a decrease in life expectancy of up to two decades compared with the general population, with cardiovascular disease as the leading cause of death. SMI is associated with increased cardiovascular risk profile and early onset of incident cardiovascular disease. Following an acute coronary syndrome, patients with SMI have a worse prognosis, but are less likely to receive invasive treatment. In this narrative review, the management of coronary artery disease in patients with SMI is discussed, and avenues for future research are highlighted.

Both patients and health care providers working in mental health facilities witness high rates of incidents that have the potential to jeopardize their safety. Despite this, there are few studies that have documented the kind of incidents that are experienced, or explored the potential contributors to these incidents, and solutions that would result in better safety. This study explored various types of safety related incidents occurring in mental facilities in Kenya, perceived contributing factors, and recommendations for improve.

This qualitative descriptive study was carried out between December 2019 - February 2020. It included 28 mental health staff across 14 mental health unit spread across the country.

All the participants reported having personally experienced an incident that threatened their safety or that of the patients. Most of the respondents (24/26. 91.67%) admitted to have experienced verbal aggression while 54.17%, (n = 24) had experienced physical assault. Participating health care workers attributed the safety incidents to poor infrastructure, limited human resources, and inadequate medication to calm down agitated patients. Suggested solutions to improve patient safety included; improving surveillance systems, hiring more specialized healthcare workers, and provision of adequate supplies such as short-acting injectable psychotropic.

Incidents that threaten patient and staff safety are common in mental health facilities in Kenya. There is need to strengthen staff capacity and reporting mechanisms, as well as invest in infrastructural improvements, to safeguard patient and staff safety in mental health facilities in Kenya.

Explainable sudden deaths in schizophrenia patients due to both cardiac (SCD) and non-cardiac causes (SNCD) have been extensively documented. However, sudden unexplained death (SUD) in this cohort remains to be elucidated. This study retrospectively analyzed 18 SUD cases that underwent systematic autopsy at our institutes during the period 2010-2022. The etiological, demographic, and autopsy features of the SUD cases were then compared with 37 year-matched sudden explainable deaths (23 SCD cases and 14 SNCD cases). Our results showed that the average age of the SUD was 39.0 ( ± 8.4) years, with the disease duration of 11.8 ( ± 8.1) years and a male/female ratio of 11:7. Most cases occurred during daytime (72.2%) and outside of hospital (77.8%). A large proportion of the SUD cases (77.8%) had persistent psychiatric episodes before death. Clozapine was found to be the most commonly used antipsychotic (33.3%), followed by Olanzapine (27.8%), Risperidone (27.8%) and Chlorpromazine (27.8%) in the SUD cases. When compared among groups, the SUD cases showed significantly younger ages (p = 0.035), lower heart weight (p = 0.004) and lower proportion of Clozapine use (p = 0.045). The presence of persistent psychiatric episodes was significantly higher in the SUD group than in any explainable deaths (p = 0.018) and was an independent risk factor for SUD (OR = 4.205, p = 0.040). This is the first autopsy-based study of SUD cases from China. We conclude that a stable mental state maintained by antipsychotics (i.e., Clozapine) is vital to schizophrenia patients.

Patients with mental disorders are at increased risk of premature mortality. Psychiatric inpatients are a particularly vulnerable population, yet data on the mortality rate and causes of death among psychiatric inpatients in a national sample are scarce.

We analyzed data collected from patients who died during psychiatric hospitalization in 2019 and 2020 from 41 psychiatric hospitals in China.

In total, 719 inpatients died over the study period. There were more deaths in 2019 (N = 409, 56.9%) compared to 2020 (N = 310, 43.1%). The mean age was 73.3 ± 16.5 years old, with males significantly younger than females (71.5 ± 16.9 vs. 75.9 ± 15.6, p < 0.001). Sudden death accounted for 11.5% of all deaths. The cause was unknown for 31.2% of cases. Among those with known causes of death, respiratory disorders were most common in patients with psychotic disorders (41.9%) and mood disorders (29.8%). Suicide accounted for 17.0% of deaths in patients with mood disorders.

Patients who died during psychiatric hospitalization were overall older (>70 years), and more than one in ten died due to sudden death. While respiratory disorders accounted for the largest proportion of known causes, the causes were unknown in nearly one-third. Death due to suicide, a preventable cause, remained common among patients with mood disorders. Evidence-based interventions should be implemented.

Since the 1950 s, several studies have reported that patients using first generation and/or second-generation antipsychotics had increased risk of venous thromboembolism events. These events include deep vein thrombosis and/or pulmonary embolism (PE). However, data about fatal PE in patients on antipsychotics (APs) remain scarce. Thus, the current study aimed to investigate sociodemographic, clinical and pharmacological characteristics related to psychiatric patients on APs and who died from a fatal PE. We reported a case-series, then conducted a literature review of relevant studies and performed a meta-analysis of studies with usable data. The main outcome of the study suggested a significantly high risk of fatal PE in patients using APs compared to nonusers (Odds Ratio=6.68, with 95% confidence interval 1.43-31.11). Clozapine was the most incriminated drug. Low potency first generation APs were the second most exhibited medication. Studies about the topic remain scarce with a high heterogeneity and a high probability of bias. Further studies are needed to ascertain this risk and to establish target preventive measures in this particularly vulnerable population.

Sudden unexpected death in the young (SUDY) is a tragic event resulting in the fatality of seemingly healthy individuals between the ages of one and 40 years. Whilst studies have been performed on sudden unexpected death in infants, children, and adults respectively, little is known about trends in risk factors and causes of death of SUDY cases. Understanding the factors surrounding these deaths could lead to targeted interventions for at-risk individuals. Hence, a systematic approach to investigate the reported possible causes of SUDY was employed using three major databases and Primo, wherein 67 relevant articles were identified and 2 additional guidelines were read. Sudden unexpected death in epilepsy and sudden cardiac events were well-established causes of death with risk factors such as male predominance, substance use and a familial history identified. It was acknowledged that while the cause of death is established following post-mortem examination in many cases, some remain non-specific or undetermined. Considering the genetic etiology, these cases would be ideal candidates for molecular autopsies in the future. Thus, this review emphasized the significance of acquiring the relevant information to aid in resolving cause of death of these SUDY cases and subsequently highlighted the potential for further studies on risk factors and the value of molecular autopsies.

Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes life-shortening adverse effects. Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns. These cardiotoxic effects range from arrhythmia to heart failure in the clinic, with myocarditis/cardiomyopathy, ischemic injuries, and unexplained cardiac lesions as the pathological bases. Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity. This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level. We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity. We propose that third-generation antipsychotics or drug adjuvant therapy, such as cannabinoid receptor modulators that confer dual benefits - i.e., alleviating cardiotoxicity and improving metabolic disorders - deserve further clinical evaluation and marketing.

Oxidative stress is considered the principal mediator of myocardial injury under pathological conditions. It is well known that reactive oxygen (ROS) or nitrogen species (RNS) are involved in myocardial injury and repair at the same time and that cellular damage is generally due to an unbalance between generation and elimination of the free radicals due to an inadequate mechanism of antioxidant defense or to an increase in ROS and RNS. Major adverse cardiovascular events are often associated with drugs with associated findings such as fibrosis or inflammation of the myocardium. Despite efforts in the preclinical phase of the development of drugs, cardiotoxicity still remains a great concern. Cardiac toxicity due to second-generation antipsychotics (clozapine, olanzapine, quetiapine) has been observed in preclinical studies and described in patients affected with mental disorders. A role of oxidative stress has been hypothesized but more evidence is needed to confirm a causal relationship. A better knowledge of cardiotoxicity mechanisms should address in the future to establish the right dose and length of treatment without impacting the physical health of the patients.

Psychiatric patients have increased risk of deep vein thrombosis (DVT). However, there is no systematic data on risk assessment of DVT among psychiatric inpatients. The aim of this study was to develop a risk stratification scoring system for DVT among psychiatic patients on admission.

A systematic review of psychiatric patient's charts, who were admitted to the Tokyo Metropolitan Matsuzawa Hospital from June 2012 to February 2016 and underwent screening for DVT, was conducted. Patients were randomly divided into development (n = 2634) and validation (n = 2634) groups. Estimated risk values in the multiple logistic regression model for the development sample were rounded to the nearest integer, and used as points of associated factors in the risk stratification scoring system; the total scores were tested in the validation sample. The score's discriminatory ability was assessed with the area under the receiver operating characteristic curve (AUC).

Among the 5268 patients, 258 (4.9%) had DVT. Advancing age, female sex, active cancer, previous venous thromboembolism, transfer from a general hospital, catatonia, and major depressive episode were all significantly associated with the presence of DVT in the development sample. The total score showed good discriminatory ability in the validation sample (AUC: 0.816, 95% confidence interval: 0.781-0.851); scores of 0-1, 2-3, 4-5, and ≥ 6 were associated with very low risk (0.7%), low risk (4.6%), moderate risk (14.9%), and high risk (35%) for DVT, respectively.

Our risk stratification scoring system showed good performance for detection of DVT among psychiatric patients on admission.

The pathogenesis of sudden cardiac death may differ between younger and older adults in schizophrenia, but evidence remains scant. This study investigated the age effect on the incidence and risk of the physical and psychiatric comorbidity for sudden cardiac death.

Using 2000 to 2016 data from the Taiwan National Health Insurance Research Database and Department of Health Death Certification System, we identified a national cohort of 170,322 patients with schizophrenia, 1,836 of whom had a sudden cardiac death. Standardized mortality ratios (SMRs) were estimated. Hazard ratios and population attributable fractions of distinctive comorbidities for sudden cardiac death were assessed.

The SMRs of sudden cardiac death were all >1.00 across each age group for both sexes, with the highest SMR in male patients aged <35 years (30.88, 95% CI: 26.18-36.18). The fractions of sudden cardiac death attributable to hypertension and congestive heart failure noticeably increased with age. By contrast, the fraction attributable to drug-induced mental disorder decreased with age. Additionally, chronic hepatic disease and sleep disorder increased the risk of sudden cardiac death in patients aged <35 years. Dementia and organic mental disorder elevated the risk in patients aged between 35-54 years. Ischemic heart disease raised the risk in patients aged ≥55 years.

The risk is increased across the lifespan in schizophrenia, particularly for younger male patients. Furthermore, physical and psychiatric comorbidities have age-dependent risks. The findings suggest that prevention strategies targeted toward sudden cardiac death in patients with schizophrenia must consider the age effect.

A major depressive episode is a risk factor for venous thromboembolism (VTE) in psychiatric inpatients. However, it is unclear whether the severity of depressive symptoms or duration of the current depressive episode is associated with VTE. Further, the VTE prevalence among hospitalized patients with a major depressive episode receiving electroconvulsive therapy is unknown. This retrospective study examined factors associated with VTE among hospitalized patients with a major depressive episode and estimated the prevalence of VTE in such patients who underwent electroconvulsive therapy.

Patients with a major depressive episode hospitalized in the Department of Neuropsychiatry at Akita University Hospital between January 2018 and December 2020 were included. Data from the first week of hospitalization were extracted from medical records. VTE was diagnosed based on the findings of computed tomography. To evaluate whether the severity of depressive symptoms or duration of the current depressive episode was associated with VTE, logistic regression analysis was conducted after adjusting for covariates with known VTE risk factors (antidepressants, antipsychotics, and physical comorbidities).

We analyzed 133 patients; of these, 14 were diagnosed with asymptomatic VTE. The severity of depressive symptoms (odds ratio: 1.220, 95% confidence interval: 1.081-1.377, p = 0.001) was significantly associated with VTE. The prevalence of VTE among those receiving electroconvulsive therapy was 35% (7/20).

The prevalence of VTE was 35% among patients receiving in-hospital electroconvulsive therapy for a major depressive episode. VTE should be considered for hospitalized patients with severe depressive symptoms and patients receiving in-hospital electroconvulsive therapy for a major depressive episode.

Research regarding the effects of age in patients with schizophrenia taking antipsychotics on the risk of sudden cardiac death is lacking. We determined the effect of patient age on the association between exposure to antipsychotics and the risk of sudden cardiac death in a nationwide schizophrenia cohort.

From the Taiwan National Health Insurance Research Database and Department of Health Death Certification System, data of 1836 patients with schizophrenia who had experienced sudden cardiac death between 2000 and 2016 were included. A case-crossover design by using a 14-day window was applied, and subgroup analyses were performed by stratifying patients into three age subgroups (<45, 45-65, and >65 years) to assess the effect of age on the risk of sudden cardiac death in patients taking antipsychotics.

No association between exposure to antipsychotic agents and sudden cardiac death risk was found in patients aged >65 years who were characterized by a high burden of medical illnesses. However, zotepine significantly increased the risk of sudden cardiac death in patients aged <45 years (adjusted relative risk [RR] = 2.68, P = 0.046). Flupentixol (adjusted RR = 5.30, P = 0.004) and risperidone (adjusted RR = 1.68, P = 0.01) significantly elevated the risk of sudden cardiac death in patients aged 45-65 years.

This study suggests that individual antipsychotics pose different risks of sudden cardiac death in patients with schizophrenia across their lifespan. Clinicians should consider patient age when evaluating the risks and benefits of antipsychotic treatment.

Abnormal autonomic nervous system (ANS) function may result in poor outcomes in patients with schizophrenia. Altered cardio-respiratory coupling, which indicates suppression of vagal activity, was identified as an important trait in patients with schizophrenia and their unaffected relatives. Heart rate variability (HRV) in standardized bedside reflex tests has been studied, mostly in medicated patients with schizophrenia whose ANS function could be influenced by medication. Our study aimed to explore the autonomic function differences between drug-naïve patients with schizophrenia and healthy individuals during challenge tests combining respiration and HRV analysis. Forty-two drug-naïve patients with schizophrenia were matched with 42 healthy controls in terms of age and gender. Their beat-to-beat blood pressure and heart rate were monitored in the supine position as a survey of ANS function, and the mean heart rate range (MHRR) was measured under deep-breathing challenge. A decreased MHRR, a sensitive sign indicating an impaired parasympathetic response, during the deep-breathing challenge among the drug-naïve patients with schizophrenia was found. Drug-naïve patients with schizophrenia may have a parasympathetic dysfunction in the early stages of schizophrenia before medication is introduced, which could be considered a neurobiological marker in the pathophysiology of schizophrenia.

Data on the incidence and risk factors of sudden cardiac death in patients with bipolar disorder are lacking in the literature.

By using data from the Taiwan National Health Insurance Research Database and Department of Health Death Certification System between 2000 and 2016, we conducted a prospective national cohort study to determine the incidence and risk factors of sudden cardiac death in bipolar disorder patients. The study cohort included 46,490 patients with bipolar disorder, 467 of whom experienced sudden cardiac death.

Stratified analyses showed that the standardized mortality ratios (SMRs) of sudden cardiac death were all above 1.00 across each age interval, with the highest SMR in patients aged <30 years (31.96, 95% CI: 20.47-47.55). Notably, hypertension raised the risk of sudden cardiac death in both patients aged <50 years (1.85, 95% CI: 1.23-2.79) and aged ≥50 years (1.44, 95% CI: 1.14-1.83). In addition, venous and lymphatic disorders (1.97, 95% CI: 1.23-3.16), and alcohol use-related disorder (2.34, 95% CI: 1.62-3.38) elevated the risk of sudden cardiac death in patients aged <50 years. Congestive heart failure (1.59, 95% CI: 1.13-2.23) and dementia (1.75, 95% CI: 1.30-2.35) increased the risk of sudden cardiac death in patients aged ≥50 years.

The risk of sudden cardiac death is remarkably high in bipolar disorder patients across the lifespan. Prevention strategies specific to individuals with bipolar disorder are urgently required.

This is a report of a joint World Psychiatric Association/International College of Neuropsychopharmacology (WPA/CINP) workgroup concerning the risk/benefit ratio of antipsychotics in the treatment of schizophrenia. It utilized a selective but, within topic, comprehensive review of the literature, taking into consideration all the recently discussed arguments on the matter and avoiding taking sides when the results in the literature were equivocal. The workgroup's conclusions suggested that antipsychotics are efficacious both during the acute and the maintenance phase, and that the current data do not support the existence of a supersensitivity rebound psychosis. Long-term treated patients have better overall outcome and lower mortality than those not taking antipsychotics. Longer duration of untreated psychosis and relapses are modestly related to worse outcome. Loss of brain volume is evident already at first episode and concerns loss of neuropil volume rather than cell loss. Progression of volume loss probably happens in a subgroup of patients with worse prognosis. In humans, antipsychotic treatment neither causes nor worsens volume loss, while there are some data in favor for a protective effect. Schizophrenia manifests 2 to 3 times higher mortality vs the general population, and treatment with antipsychotics includes a number of dangers, including tardive dyskinesia and metabolic syndrome; however, antipsychotic treatment is related to lower mortality, including cardiovascular mortality. In conclusion, the literature strongly supports the use of antipsychotics both during the acute and the maintenance phase without suggesting that it is wise to discontinue antipsychotics after a certain period of time. Antipsychotic treatment improves long-term outcomes and lowers overall and specific-cause mortality.

Patients with serious mental illness (SMI) have an increased risk of sudden death. Higher rates of signal-averaged electrocardiogram (SAECG) abnormal late potentials (LP), which may be a predictor of sudden death risk, have been shown in patients with schizophrenia. We aimed to assess the prevalence and predictors of electrocardiograph (ECG) and SAECG abnormalities in a mixed SMI population.

Consecutive consenting inpatients with SMI had 12-lead ECG and SAECG recorded in addition to demographics, diagnoses and medications. Standard criteria for abnormal SAECG were applied. Multivariate regression analysis was performed to determine predictors of SAECG abnormalities including diagnoses, body mass index, ECG parameters, psychotropic medication use, and medications associated with Long QT or Brugada syndromes.

Eighty (80) patients, 49% male, mean age 39±17 years were included. SAECG criteria abnormality for 1, 2 or 3 criteria were seen in 19, 3 and 5 cases (34% in total) respectively. Early repolarisation pattern was seen in 19% of patients. SAECG abnormality was associated with male gender (OR 7.3; 95% CI 2.3-23.4), and schizophrenia/schizoaffective disorder diagnosis (OR 7.4; 95% CI 1.9-29.0), but not with medication type or dose.

In the mixed SMI population studied, there was a high rate of SAECG-detected late potentials (34%) and early repolarisation pattern (19%). Schizophrenia/schizoaffective disorder diagnosis was the strongest multivariate predictor identified. Further studies are needed to define the mechanism and significance of these cardiac abnormalities in SMI patients.

This case report highlights the rare occurrence of postpartum psychosis in the setting of peripartum cardiomyopathy, which can have rare presentations like arrhythmias and pulmonary edema; and the challenges one should anticipate while managing these conditions together. Caution is advised whenever antipsychotic drugs are to be administered to a patient with a cardiac condition as these drugs potentially increase the risk of arrhythmias and sudden death.

A 35 year old grand multiparous woman who was 1 week into puerperium was admitted with severe difficulty in breathing at rest, chest congestion and pain. She also had easy fatigability, orthopnea, paroxysmal nocturnal dyspnea, edema, tachycardia, tachypnea, irregularly irregular heart rate with a pulse deficit, elevated jugular venous pressure, cardiomegaly, hepatomegaly and pulmonary crepitations. On the sixth day while improving on standard drugs for heart failure, she developed bizarre behavior and confusion. She also had auditory, visual and olfactory hallucinations; violence to the baby and the husband; and refusal to feed and take medication. There was no altered sensorium and the vital signs were normal. She was diagnosed with puerperal psychosis during the management of peripartum cardiomyopathy.

In the rare occurrence of puerperal psychosis in the course of management of peripartum cardiomyopathy one must be acutely aware of the risk of sudden cardiac death occasioned by use of antipsychotics, either directly or due to arrhythmias. Continuous electrocardiogram (ECG) monitoring or use of alternative management modalities is thus highly advised.

While depression has been recognized as a risk factor for venous thromboembolism (VTE), the prevalence of VTE in depressed inpatients has never been investigated. The aim of this study was thus to examine VTE prevalence and factors associated with VTE in depressed inpatients.

We conducted a retrospective cross-sectional study of consecutive depressed inpatients (n = 94) from January 1, 2018, to June 30, 2019, at the psychiatry department of Akita University Hospital. As part of our clinical routine, depressed inpatients were screened for VTE using D-dimer, and patients who screened positive underwent enhanced CT to examine VTE. A variety of data was extracted from medical records, including, amongst others, age, sex, body mass index, diagnoses of psychiatric disorders, total scores on the 17-item Hamilton Depression Rating Scale, duration of current depressive episode, daily dosages of antidepressants and antipsychotics, catatonia, and physical restraint.

VTE was detected in 8.5% of depressed inpatients. There were no significant differences between VTE-positive and VTE-negative inpatients regarding any of the considered factors.

Our analysis shows a VTE prevalence of 8.5% in depressed inpatients, higher than that of 2.3% reported in a previous study in hospitalized patients with psychiatric disorders including depression. This emphasizes the importance of VTE screening for depressive inpatients.

These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.

Schizophrenia is a detrimental psychiatric disorder, with an increased mortality from natural and nonnatural causes.

This study was a retrospective review of autopsy cases of all the individuals with history of schizophrenia investigated by the Office of the Chief Medical Examiner, State of Maryland, for a 5-year period from 2008 to 2012.

A total of 391 schizophrenia patients were autopsied at the Office of the Chief Medical Examiner because they died suddenly and unexpectedly. Their age ranged from 15 to 100 years with the mean age of 49.5 years. Of the 391 deaths, 191 (48.8%) were white, 185 (47.3%) were African American, and 15 (3.9%) were either Hispanic or Asian. The male and female ratio was 1.5:1. The majority of deaths (64.2%) were caused by natural diseases, 12.0% deaths were accidents, 11.5% deaths were suicides, and 9.7% deaths were homicides. The manner of death remained undetermined in 38 cases (9.7%). Of the 251 natural deaths, 198 cases (78.9%) were owing to cardiovascular diseases. Cause of death was listed as cardiac arrhythmia in 11 cases. This diagnosis of cardiac arrhythmia was made by exclusion based on death scene investigation, review of medical history, complete autopsy, and toxicological tests. Drug intoxication was the second most common cause of death.

The study shows high fatality caused by cardiovascular diseases and drug intoxication among schizophrenia patients, which calls attention of the medical community to closely monitor the high risk factors of sudden death among schizophrenia patients.

Although sudden cardiac deaths are more common in psychiatric patients than the general population, data on their causes are very limited. The aim of this study was to investigate initial rhythms and causes of out-of-hospital cardiac arrest (OHCA) in patients with psychiatric disorders.

We conducted a systematic chart review of patients resuscitated after OHCA and hospitalized in the Tertiary Emergency Medical Center of Tokyo Metropolitan Bokutoh Hospital in Japan between January 2010 and December 2017. The initial rhythms and causes of OHCA were compared between psychiatric patients and non-psychiatric patients. Parameters of interest were compared using chi-squared test, Fisher's exact test, or the Mann-Whitney U-test, as appropriate.

A total of 49 psychiatric and 600 non-psychiatric patients were eligible for this study. Fatal but shockable arrhythmias (i.e. ventricular fibrillation and ventricular tachycardia) were less frequently observed as initial rhythms in patients with psychiatric disorders than the others (22.4% vs 49.7%, P < 0.001). Cardiac origin was less common as the cause of OHCA (26.5% vs 58.5%, P < 0.01), while airway obstruction and pulmonary embolism were more frequent in psychiatric versus non-psychiatric patients (24.5% vs 6.5%, P < 0.01; and 12.2% vs 1.5%, P < 0.01, respectively). The results were similar when psychiatric patients were compared with sex- and age-matched controls selected from the non-psychiatric patient group.

Although fatal arrhythmias may be less common, non-cardiac causes such as pulmonary embolism and airway obstruction need to be treated with high clinical suspicion in an event of sudden cardiac arrest in psychiatric patients.

Certain psychotropics and a number of other medications used to treat medical conditions in psychiatric patients can increase the risk of prolonging the corrected QT (QTc) interval on the electrocardiogram, which puts patients at risk of life-threatening ventricular arrhythmias such as torsades de pointes. Pharmacists are often consulted about medications which are known to prolong the QTc interval. Although this information is often accessible, advising how to identify, assess, manage, and refer psychiatric patients at risk for drug-induced QTc prolongation is more challenging.

The objective of this project was first to review the literature, which describes guidelines and recommendations for the assessment and management of drug-induced QTc prolongation, and then to design an algorithm to be used by pharmacists working closely with mental health professionals or who provide care to psychiatric patients.

A review of the literature was undertaken. Predefined keywords were used to perform the database search in MEDLINE, EMBASE, and International Pharmaceutical Abstracts to identify reviews, reports and guidelines on the assessment, prevention and monitoring of drug-induced QTc prolongation with an emphasis on psychotropic medications and management in the psychiatric population.

The electronic database search retrieved 637 relevant citations. These were initially screened by title and all duplicates were removed. The abstracts were then reviewed for relevancy based on the inclusion/exclusion criteria. Additional citations were retrieved from the bibliography of the articles identified in the initial search. A total of 79 articles describing QTc prolongation in the psychiatric population were thoroughly examined, but only 31 articles were selected to guide the development of the algorithm.

The literature-based algorithm developed provides a stepped-based approach for the assessment, monitoring, and management of drug-induced QTc prolongation in the psychiatric population. The algorithm may assist mental health clinicians in the decision-making process when psychiatric patients are prescribed medications known to increase the QTc interval.

To examine the recent literature regarding sudden death in patients with schizophrenia and synthesize salient conclusions based on this evidence.

Sudden cardiac death (SCD) is the largest subset of sudden unexpected death (SUD), with up to 40% of SUD from cardiovascular causes. SCD has been associated with exposure to both first and second-generation antipsychotics. Clozapine [odds ratio (OR) 3.67, 95% confidence interval (CI) 1.94-6.94] confers the highest risk of SCD followed by risperidone (OR 3.04, 95% CI 2.39-3.86) then olanzapine (OR 2.04, 95% CI 1.52-2.74). SCD not associated with antipsychotic use has been correlated to several modifiable and nonmodifiable risk factors - obesity, smoking, dyslipidemia, diabetes, hypertension, age, sex, and history of cardiovascular disease. Other subsets of SUD include hematological and pulmonary causes, including agranulocytosis leading to sepsis, deep vein thrombosis leading to pulmonary embolisms, and aspiration pneumonia leading to sepsis.

There is a huge paucity in genetic and pharmacogenetic data focused on SUD in schizophrenia. Future studies should emphasize the genetic aspects as well as clarify the underlying molecular mechanisms of these pathways. Additionally, early detection of those patients at high risk for SUD and discovery of preventive measures should also be emphasized.

Venous thromboembolism (VTE) is the combination of pulmonary embolism (PE) and deep vein thrombosis. In recent years, VTE has been gaining attention in the field of psychiatry as it can cause sudden deaths in patients hospitalized in psychiatric departments. The purpose of this study was to investigate the incidence of VTE in psychiatric inpatients using contrast-enhanced computed tomography (CT).

At the psychiatric department of the Akita University Hospital, NANOPIA^® D-dimer was measured in patients with suspected symptomatic VTE or believed to be at risk for asymptomatic VTE. A follow-up contrast-enhanced CT was also performed in cases of D-dimer values over 1 µg/mL. Patients diagnosed with VTE based on contrast-enhanced CT during hospitalizations between May 1, 2009 and April 30, 2017 were analyzed. VTE incidence was compared in restrained and unrestrained catatonic and noncatatonic patients. We also investigated whether VTE was symptomatic or asymptomatic as well as its outcomes.

The overall incidence of VTE was 2.3% (39/1,681) in the 8-year period. VTE was observed in 61.1% (11/18) of catatonic patients, 4.1% (11/270) of noncatatonic restrained patients, and 1.2% (17/1,393) of noncatatonic unrestrained patients. PE was observed in 76.9% (30/39) of VTE patients and 97.4% (38/39) of VTE patients were asymptomatic. Recovery was achieved in all cases of VTE treated with anticoagulation therapy.

These results indicate that the risk of VTE is high in psychiatric inpatients and that PE is common in these population. The data may also suggest that contrast-enhanced CT is important in surveying thrombus in suspected cases of VTE. In the psychiatric field, proper attention must be given to VTE, regardless of the presence or absence of catatonia or restraint, particularly given that PE was observed in more than 75% of cases of VTE.

The use of antipsychotic medications has now expanded to multiple mental health conditions beyond schizophrenia. This has increased the overall population exposure to these medications, which have been associated with both metabolic changes and adverse cardiovascular effects. QTc prolongation, torsades de pointes, sudden cardiac death, myocarditis, and cardiomyopathy are all very real concerns that clinicians face on a regular basis. One must take these risks into consideration when selecting antipsychotic therapy and also when determining whether therapeutic changes and adjustments are necessary. This review examines a number of cardiac-associated concerns, the role that antipsychotics may play in contributing to these adverse events, and suggested management interventions.

The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is another old antipsychotic with a long half-life so one oral dose may last up to one week. This could confer advantage.

To assess the clinical effects of chlorpromazine compared with penfluridol for adults with schizophrenia.

On 31 March 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register.

We included all randomised clinical trials focusing on chlorpromazine versus penfluridol for adults with schizophrenia or related disorders. Outcomes of interest were death, service utilisation, global state, mental state, adverse effects and leaving the study early. We included trials meeting our selection criteria and reporting useable data.

We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we planned to estimate the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.

The review includes three studies with a total of 130 participants. Short-term results for hospital admissions showed no clear difference between chlorpromazine and penfluridol (1 RCT, n = 29, RR 0.19, 95% CI 0.01 to 3.60, low-quality evidence). No clear difference in the incidence of akathisia was found at medium term (2 RCTs, n = 85, RR 0.19, 95% CI 0.04 to 1.06, low-quality evidence), and similar numbers of participants - nearly half - from each treatment group left the study early (3 RCTs, n = 130, RR 1.21, 95% CI 0.83 to 1.77, low-quality evidence). The risk of needing additional antiparkinsonian medication was less in the chlorpromazine group (2 RCTs, n = 74, RR 0.70, 95% CI 0.51 to 0.95). No useable data reported clinically important change in global or mental state. No data were reported for relapse. No deaths were reported by the trials.

Only three small studies provided data and the quality of reporting and evidence is low. Limited data indicate the efficacy and adverse effects profiles of chlorpromazine and penfluridol are generally similar. Penfluridol, however, may confer advantage by needing to be given only once per week. Firm conclusions are not possible without good-quality trials, and where these treatments are used, such trials are justified.

Obstructive sleep apnea (OSA) is a health hazard since it is associated with neurocognitive dysfunction and cardio-metabolic diseases. The prevalence of OSA among people with serious mental illness (SMI) is unclear.

We searched major electronic databases from inception till 06/2015. Articles were included that reported the prevalence of OSA determined by polysomnography (PSG) or an apnea-hypopnea index (AHI) >5 events/hr, in people with major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia. A random effects meta-analysis calculating the pooled prevalence of OSA and meta-regression of potential moderators were performed.

Twelve articles were included representing 570,121 participants with SMI (mean age=38.3 years (SD=7.5)), 45.8% male (range=32-80.4) and mean body mass index (BMI) 25.9 (SD=3.7). The prevalence of OSA in SMI in clinical studies was 25.7% (95% CI 13.9 to 42.4%, n=1,535). Higher frequencies of OSA were seen in MDD (36.3%, 19.4-57.4%, n=525) than in BD (24.5%, 95% CI 10.6-47.1, n=681) and schizophrenia (15.4%, 95% CI 5.3-37.1%, n=329). The prevalence of OSA in 568,586 people with SMI from population cohort studies was 10.7% (95% CI 2.4-37.0%) and 19.8% (95% CI 2.5-70.0%) in 358,853 people with MDD. Increasing age (β=0.063, 95% CI 0.0005-0.126, p=0.04, N=10) and BMI predicted increased prevalence of OSA (β=0.1642, 95% CI 0.004-0.3701, p=0.04, N=9).

People with SMI (particularly MDD) have a high prevalence of OSA. Screening for and interventions to manage OSA in SMI including those focused on reducing BMI are warranted.

Rapid response teams are used to improve the recognition of acute deteriorations in medical and surgical settings. They are activated by abnormal physiological parameters, symptoms or clinical concern, and are believed to decrease hospital mortality rates. We evaluated the reasons for activation and the outcome of rapid response interventions in a 222-bed psychiatric hospital in New York City using data obtained at the time of all activations from January through November, 2012. The primary outcome was the admission rate to a medical or surgical unit for each of the main reasons for activation. The 169 activations were initiated by nursing staff (78.7 %) and psychiatrists (13 %) for acute changes in condition (64.5 %), abnormal physiological parameters (27.2 %) and non-specified concern (8.3 %). The most common reasons for activation were chest pain (14.2 %), fluctuating level of consciousness (9.5 %), hypertension (9.5 %), syncope or fall (8.9 %), hypotension (8.3 %), dyspnea (7.7 %) and seizures (5.9 %). The rapid response team transferred 127 (75.2 %) patients to the Emergency Department and 46 (27.2 %) were admitted to a medical or surgical unit. The admission rates were statistically similar for acute changes in condition, abnormal physiological parameters, and clinicians' concern. In conclusion, a majority of rapid response activations in a self-standing psychiatric hospital were initiated by nursing staff for changes in condition, rather than for policy-specified abnormal physiological parameters. The findings suggest that a rapid response system may empower psychiatric nurses to use their clinical skills to identify patients requiring urgent transfer to a general hospital.

Treatment with haloperidol has been shown, in studies using death certificates and prescription files, to be associated with an excess of sudden cardiac deaths, and regulatory warnings highlight this risk in patients with dementia. We used autopsy findings to determine whether the rate of sudden cardiac death is greater in cases of unexpected deaths of patients with dementia treated with haloperidol.

From 1989 through 2013, 1219 patients with a primary diagnosis of dementia with behavioral disturbance were admitted to a psychiatric hospital, and 65 (5.3%) died suddenly. Sixty-five patients (5.3%) died unexpectedly. Complete post-mortem examinations after the sudden death were performed in 55 (84.6%) patients. Twenty-seven of the autopsied cases (49.1%) had been treated with haloperidol orally (2.2 mg ± 2.1 mg/day), the only antipsychotic used in this cohort. Univariable comparisons and multivariable regression analyses compared the groups of patients with or without sudden cardiac death.

The leading causes of death were sudden cardiac death (32.7%), myocardial infarction (25.5% of patients), pneumonia (23.6%), and stroke (10.9%). Patients with sudden cardiac death and those with anatomically established cause of death were similar regarding the use of haloperidol (p = 0.5). Sudden cardiac death patients were more likely to suffer from Alzheimer's dementia (p = 0.027) and to have a past history of heart disease (p = 0.0094), and less likely to have been treated with a mood stabilizer (p = 0.024), but none of these variables were independent predictors of sudden cardiac death.

Autopsy data suggest that oral haloperidol is not associated with increased risk of sudden cardiac death in psychiatric inpatients with dementia.

The majority of excess mortality among people with schizophrenia seems to be caused by cardiovascular complications, and in particular, coronary heart disease. In addition, the prevalence of heart failure and arrhythmias is increased in this population. Reduced efferent vagal activity, which has been consistently described in these patients and their healthy first-degree relatives, might be one important mechanism contributing to their increased cardiac mortality. A decrease in heart rate variability and complexity was often shown in unmedicated patients when compared to healthy controls. In addition, faster breathing rates, accompanied by shallow breathing, seem to influence autonomic cardiac functioning in acute unmedicated patients substantially. Moreover, low-physical fitness is a further and independent cardiac risk factor present in this patient population. Interestingly, new studies describe chronotropic incompetence during physical exercise as an important additional risk factor in patients with schizophrenia. Some studies report a correlation of the autonomic imbalance with the degree of positive symptoms (i.e., delusions) and some with the duration of disease. The main body of psychiatric research is focused on mental aspects of the disease, thereby neglecting obvious physical health needs of these patients. Here, a joint effort is needed to design interventional strategies in everyday clinical settings to improve physical health and quality of life.

The clinical presentation of panic disorder and panic attack overlaps many symptoms typically experienced in coronary heart disease (CHD). Etiological links between panic disorder and CHD are controversial and remain largely tenuous. This systematic review aims to pool together data regarding panic disorder with respect to incident CHD or myocardial infarction.

Electronic databases (MEDLINE, EMBASE, PsycINFO and SCOPUS) will be searched using a search strategy exploding the topics for CHD and panic disorder. Authors and reference lists of included studies will also be contacted to identify additional published and unpublished studies. Eligibility criteria are as follows:

persons without CHD who meet criteria for panic disorder, panic attack, anxiety neurosis or elevated panic disorder symptoms; Comparison: persons without CHD who do not meet criteria for panic disorder, panic attack, anxiety neurosis or elevated panic disorder symptoms;

verified fatal and non-fatal CHD at follow-up; including coronary revascularization procedure, coronary artery disease, and myocardial infarction. Studies adopting self-report CHD will be ineligible. Screening will be undertaken by two independent reviewers with disagreements resolved through discussion. Data extraction will include original data specified as hazard ratios, risk ratios, and original cell data if available. Risk of bias assessment will be undertaken by two independent reviewers. Meta-analytic methods will be used to synthesize the data collected relating to the CHD outcomes with Cochrane Review Manager 5.3.

This systematic review aims to clarify whether panic disorder is associated with elevated risk for subsequent CHD. An evaluation of the etiological links between panic disorder with incident CHD might inform evidence-based clinical practice and policy concerning triaging chest pain patients, diagnostic assessment, and psychiatric intervention with panic disorder patients.

PROSPERO CRD42014014891 .

To investigate the association between acute myocardial infarction (AMI) and recent exposure to antipsychotic agents in people with serious mental illness (SMI), and modifying influences.

A case-crossover design was applied using the Taiwan National Health Insurance Research Database (NHIRD) to compare the exposure frequency of antipsychotic agents within individuals of schizophrenia or bipolar disorder between 60-day case and control periods prior to their first AMI episode during 1996-2007.

A sample of 834 patients with incident AMI was analysed. AMI was significantly associated with more recent antipsychotic exposure in schizophrenia after adjustment (OR 1.87, 95% confidence interval 1.15-3.03) bipolar disorder (OR 1.06, 0.51-2.21). This association in schizophrenia was significantly stronger in men and in patients without previous diagnoses of cardiovascular risk factors.

These findings are consistent with a short-term risk effect of antipsychotic exposure on risk of AMI and identify potentially vulnerable groups. Further research is required to clarify underlying biological mechanisms.

The beta isoform of Neuregulin-1 (NRG-1β), along with its receptors (ErbB2-4), is required for cardiac development. NRG-1β, as well as the ErbB2 and ErbB4 receptors, is also essential for maintenance of adult heart function. These observations have led to its evaluation as a therapeutic for heart failure. Animal studies and ongoing clinical trials have demonstrated beneficial effects of two forms of recombinant NRG-1β on cardiac function. In addition to the possible role for recombinant NRG-1βs as heart failure therapies, endogenous NRG-1β/ErbB signaling appears to play a role in restoring cardiac function after injury. The potential mechanisms by which NRG-1β may act as both a therapy and a mediator of reverse remodeling remain incompletely understood. In addition to direct effects on cardiac myocytes NRG-1β acts on the vasculature, interstitium, cardiac fibroblasts, and hematopoietic and immune cells, which, collectively, may contribute to NRG-1β's role in maintaining cardiac structure and function, as well as mediating reverse remodeling.

Schizophrenia is associated with premature mortality and a high rate of sudden, unexpected deaths. Autopsy data are scant, and in studies using death certificates or root cause assessments, a majority of sudden deaths remained unexplained. In the community, post-mortem data indicate that the most common cause of sudden "natural" death is coronary artery disease. In this study, we used autopsy findings to determine the cause of sudden death in a consecutive cohort of 7189 schizophrenia patients admitted to a free-standing, psychiatric teaching hospital from 1989 to 2013. Medical record review identified 57 patients (0.79%) who died suddenly and unexpectedly during hospitalization. Autopsies were performed in 51 (89.5%) patients (55.9±9.4years, male=56.9%). Autopsy-based causes of sudden death were most commonly cardiovascular disorders (62.8%). Specific causes included myocardial infarction (52.9%), pneumonia (11.8%), airway obstruction (7.8%), myocarditis (5.9%), and dilated cardiomyopathy, hemopericardium, pulmonary embolus, hemorrhagic stroke and brain tumor (2.0% each). The sudden death remained unexplained in 6 (11.8%) patients, 3 of whom had evidence of coronary arteriosclerosis on autopsy. Patients with and without myocardial infarction were similar regarding age, gender, smoking, body mass index and psychotropic treatment (p values≥0.10). In conclusion, sudden cardiac death occurs at a 0.8% rate in a psychiatric hospital, well above general population rates. Autopsy findings indicate that sudden death in schizophrenia is caused by structural cardiovascular, respiratory and neurological abnormalities, with most cases due to acute myocardial infarction. Early recognition and treatment of coronary artery disease must become a clinical priority for all adults with schizophrenia.

Schizophrenia is a major psychotic disorder with significant comorbidity and mortality. Patients with schizophrenia are said to suffer more type-2 diabetes mellitus (T2DM) and diabetogenic complications. However, there is little consistent evidence that comorbidity with physical diseases leads to excess mortality in schizophrenic patients. Consequently, we investigated whether the burden of physical comorbidity and its relevance on hospital mortality differed between patients with and without schizophrenia in a 12-year follow-up in general hospital admissions. During 1 January 2000 and 31 June 2012, 1418 adult patients with schizophrenia were admitted to three General Manchester NHS Hospitals. All comorbid diseases with a prevalemce ≥1% were compared with those of 14,180 age- and gender-matched hospital controls. Risk factors, i.e. comorbid diseases that were predictors for general hospital mortality were identified using multivariate logistic regression analyses. Compared with controls, schizophrenic patients had a higher proportion of emergency admissions (69.8 vs. 43.0%), an extended average length of stay at index hospitalization (8.1 vs. 3.4 days), a higher number of hospital admissions (11.5 vs. 6.3), a shorter length of survival (1895 vs. 2161 days), and a nearly twofold increased mortality rate (18.0 vs. 9.7%). Schizophrenic patients suffered more depression, T2DM, alcohol abuse, asthma, COPD, and twenty-three more diseases, many of them diabetic-related complications or other environmentally influenced conditions. In contrast, hypertension, cataract, angina, and hyperlipidaemia were less prevalent in the schizophrenia population compared to the control population. In deceased schizophrenic patients, T2DM was the most frequently recorded comorbidity, contributing to 31.4% of hospital deaths (only 14.4% of schizophrenic patients with comorbid T2DM survived the study period). Further predictors of general hospital mortality in schizophrenia were found to be alcoholic liver disease (OR = 10.3), parkinsonism (OR = 5.0), T1DM (OR = 3.8), non-specific renal failure (OR = 3.5), ischaemic stroke (OR = 3.3), pneumonia (OR = 3.0), iron-deficiency anaemia (OR = 2.8), COPD (OR = 2.8), and bronchitis (OR = 2.6). There were no significant differences in their impact on hospital mortality compared to control subjects with the same diseases except parkinsonism which was associated with higher mortality in the schizophrenia population compared with the control population. The prevalence of parkinsonism was significantly elevated in the 255 deceased schizophrenic patients (5.5 %) than in those 1,163 surviving the study period (0.8 %, OR = 5.0) and deceased schizophrenic patients had significantly more suffered extrapyramidal symptoms than deceased control subjects (5.5 vs. 1.5 %). Therefore patients with schizophrenia have a higher burden of physical comorbidity that is associated with a worse outcome in a 12-year follow-up of mortality in general hospitals compared with hospital controls. However, schizophrenic patients die of the same physical diseases as their peers without schizophrenia. The most relevant physical risk factors of general hospital mortality are T2DM, COPD and infectious respiratory complications, iron-deficiency anaemia, T1DM, unspecific renal failure, ischaemic stroke, and alcoholic liver disease. Additionally, parkinsonism is a major risk factor for general hospital mortality in schizophrenia. Thus, optimal monitoring and management of acute T2DM and COPD with its infectious respiratory complications, as well as the accurate detection and management of iron-deficiency anaemia, of diabetic-related long-term micro- and macrovascular complications, of alcoholic liver disease, and of extrapyramidal symptoms are of utmost relevance in schizophrenia.

Schizophrenia is among the major causes of disability worldwide and the mortality from cardiovascular disease (CVD) is significantly elevated. There is a growing concern that this health challenge is not fully understood and efficiently addressed.

Non-systematic review using searches in PubMed on relevant topics as well as selection of references based on the authors' experience from clinical work and research in the field.

In most countries, the standardized mortality rate in schizophrenia is about 2.5, leading to a reduction in life expectancy between 15 and 20 years. A major contributor of the increased mortality is due to CVD, with CVD mortality ranging from 40 to 50% in most studies. Important causal factors are related to lifestyle, including poor diet, lack of physical activity, smoking, and substance abuse. Recent findings suggest that there are overlapping pathophysiology and genetics between schizophrenia and CVD-risk factors, further increasing the liability to CVD in schizophrenia. Many pharmacological agents used for treating psychotic disorders have side effects augmenting CVD risk. Although several CVD-risk factors can be effectively prevented and treated, the provision of somatic health services to people with schizophrenia seems inadequate. Further, there is a sparseness of studies investigating the effects of lifestyle interventions in schizophrenia, and there is little knowledge about effective programs targeting physical health in this population.

The risk for CVD and CVD-related deaths in people with schizophrenia is increased, but the underlying mechanisms are not fully known. Coordinated interventions in different health care settings could probably reduce the risk. There is an urgent need to develop and implement effective programs to increase life expectancy in schizophrenia, and we argue that mental health workers should be more involved in this important task.

Schizophrenia is a devastating mental disorder, associated with mortality rates up to three times higher than those in the general population. This post-mortem study sought to investigate the causes of death in a consecutive series of schizophrenia cases, with a specific focus on cardiovascular disease and sudden death. A 10-year review of autopsies in schizophrenia related-cases performed at the Department of Forensic Medicine in Sydney, Australia was undertaken. Premorbid clinical and demographic information was recorded, as well as the key pathological findings and final cause of death. From 2003 to 2012, there were 19,478 postmortem examinations performed of which 683 (3.5%) were deaths in people with a history of schizophrenia. In these cases, the mean age at death was 51years (range 18-93years), with 43% in the 41-60year age group. Males comprised 67% of cases. Overall, 62% of cases had a BMI≥25kg/m(2), indicating overweight or obese individuals. The three primary causes of death were "cardiovascular" (23%), "suicide" (20%), and "drug toxicity" (17%). In 11% of cases (n=72), no definitive cause of death was found, the so-called "unexplained" cases. In conclusion, patients with schizophrenia have premature mortality. The major contributing factors include cardiovascular diseases, suicide and drug toxicity. The "unexplained" and frequently sudden deaths may suggest underlying cardiac arrhythmias as a cause of death in a subgroup of schizophrenia patients.

Both schizophrenia and epilepsy have been linked to increased risk of sudden cardiac death (SCD). We hypothesized that DNA variants within genes previously associated with schizophrenia and epilepsy may contribute to an increased risk of SCD.

To investigate the contribution to SCD susceptibility of DNA variants previously implicated in schizophrenia and epilepsy.

From the ongoing Oregon Sudden Unexpected Death Study, comparisons were performed among 340 SCD cases presenting with ventricular fibrillation and 342 controls. We tested for the association between 17 single-nucleotide polymorphisms (SNPs) mapped to 14 loci previously implicated in schizophrenia and epilepsy by using logistic regression and assuming additive, dominant, and recessive genetic models.

The minor allele of the nonsynonymous SNP rs10503929 within the neuregulin 1 gene was associated with SCD under all 3 investigated models, with the strongest association for the recessive genetic model (recessive P = 4.01 × 10(-5), odds ratio [OR] 4.04; additive P = 2.84 × 10(-7), OR 1.9; and dominant P = 9.01 × 10(-6), OR 2.06). To validate our findings, we further explored the association of this variant in the Harvard Cohort SCD study. The SNP rs10503929 was associated with an increased risk of SCD under the recessive genetic model (P = .0005, OR 2.7). This missense variation causes a methionine to threonine change and functional effects are currently unknown.

The observed association between a schizophrenia-related neuregulin 1 gene variant and SCD may represent the first evidence of coexisting genetic susceptibility between 2 conditions that have an established clinical overlap. Further investigation is warranted to explore the molecular mechanisms of this variant in the pathogenesis of SCD.