Excess mortality and shortened life expectancy in people with major mental illnesses in Taiwan.

AIMS: Given the concerns of health inequality associated with mental illnesses, we aimed to reveal the extent of which general mortality and life expectancy at birth in people with schizophrenia, bipolar disorder and depressive disorder varied in the 2005 and 2010 nationally representative cohorts in Taiwan. METHODS: Two nationally representative samples of individuals with schizophrenia, bipolar disorder and depressive disorder were identified from Taiwan's national health insurance database in 2005 and 2010, respectively, and followed-up for consecutive 3 years. The database was linked to nationwide mortality registry to identify causes and date of death. Age-, gender- and cause-specific mortality rates were generated, with the average follow-up period of each age- and gender-band applied as 'weighting' for the calculation of expected number of deaths. Age- and gender-standardised mortality ratios (SMRs) were calculated for these 3-year observation periods with Taiwanese general population in 2011/2012 as the standard population. The SMR calculations were then stratified by natural/unnatural causes and major groups of death. Corresponding life expectancies at birth were also calculated by gender, diagnosis of mental disorders and year of cohorts for further elucidation. RESULTS: The general differential in mortality rates for people with schizophrenia and bipolar disorder remained wide, revealing an SMR of 3.65 (95% confidence interval (CI): 3.55-3.76) for cohort 2005 and 3.27 (3.18-3.36) for cohort 2010 in schizophrenia, and 2.65 (95% CI: 2.55-2.76) for cohort 2005 and 2.39 (2.31-2.48) for cohort 2010 in bipolar disorder, respectively. The SMRs in people with depression were 1.83 (95% CI: 1.81-1.86) for cohort 2005 and 1.59 (1.57-1.61) for cohort 2010. SMRs due to unnatural causes tended to decrease in people with major mental illnesses over the years, but those due to natural causes remained relatively stable. The life expectancies at birth for schizophrenia, bipolar disorder and depression were all significantly lower than the national norms, specifically showing 14.97-15.50 years of life lost for men and 15.15-15.48 years for women in people with schizophrenia. CONCLUSIONS: Compared to general population, the differential in mortality rates for people with major mental illnesses persisted substantial. The differential in mortality for unnatural causes of death seemed decreasing over the years, but that due to natural causes remained relatively steady. Regardless of gender, people with schizophrenia, bipolar disorder and depression were shown to have shortened life expectancies compared to general population.

Cost-effectiveness and cost-utility analysis of outpatient follow-up frequency in relation to three-year mortality in discharged patients with bipolar disorder.

There is a lack of clarity in terms of cost-effectiveness and cost-utility comparisons across different outpatient (OPD) follow-up patterns in discharged patients with bipolar disorder (BD). In this study, adult patients hospitalised for BD treatment (n = 1,591) were identified from the National Health Insurance Research Database in Taiwan. With survival as the effectiveness measure and quality-adjusted life years (QALYs) as the utility measure, a cost-effectiveness and cost-utility analysis was conducted over the 3-year follow-up period by post-discharge frequency of OPD visits. Compared to those making 1-7, 8-12 and 18 or more OPD visits, BD patients making 13-17 OPD visits within the first year after discharge had the lowest psychiatric and total healthcare costs over the follow-up period. With survival status as the effectiveness outcome, making 13-17 OPD visits was more likely to be the cost-effective option, as revealed by incremental cost-effectiveness ratios. Cost-utility analysis demonstrated that having 13-17 OPD visits was probably the more cost-effective option when considering QALYs; for instance, if society was willing to pay NTD1.5 million for one additional QALY, there was a 75.2% (psychiatric costs) to 77.4% (total costs) likelihood that 13-17 OPD visits was the most cost-effective option. In conclusion, post-discharge OPD appointments with a frequency of 13-17 visits within the first year were associated with lower psychiatric and total healthcare costs in the subsequent 3 years. Having an adequate outpatient follow-up frequency was likely to be cost-effective in the management of discharged patients with BD in this real-world setting.

Healthcare cost, service use and mortality in major psychiatric disorders in Taiwan.

BACKGROUND: We aimed to examine the differences in the cost distributions, service use, and mortality outcomes, across major psychiatric disorders in Taiwan. METHOD: A national cohort of adult patients (n = 68,068) who had newly received a diagnosis of schizophrenia, bipolar disorder, and major depressive disorder (MDD) was identified from the National Health Insurance Research Database and followed for the subsequent three years. Variations in the 1-year and 3-year healthcare cost distributions and mortality outcomes were examined according to age group (18-64 years, ≥65 years) and diagnosis. RESULTS: Regardless of age group, individuals with schizophrenia had the highest total and psychiatric healthcare costs. Healthcare costs for psychiatric services accounted for 84.25%, 60%, and 29.62% of the 1-year total healthcare costs for younger patients with a diagnosis of schizophrenia, bipolar disorder, and MDD, respectively. Psychiatric inpatient care costs constituted a major part of the 1-year psychiatric healthcare costs, e.g., 85.86% for schizophrenia patients aged 18-64 years, while psychiatric medication costs contributed to a relatively smaller part. For those older than 65 years, costs of other specialties for comorbid physical conditions were more prominent. LIMITATIONS: The perspective of the current analysis was limited to healthcare services, and we were not able to analyse wider economic impacts. CONCLUSIONS: Psychiatric inpatient care costs contributed to a significant share of psychiatric expenditures, emphasizing the need of developing strategies to reduce rehospitalisations. For those aged 65 years or older, efforts to improve interdisciplinary service care for comorbid physical conditions may be required.

Long-term antipsychotic polypharmacy prescribing in secondary mental health care and the risk of mortality.

OBJECTIVES: To investigate the association between long-term antipsychotic polypharmacy use and mortality; and determine whether this risk varies by cause of death and antipsychotic dose. METHODS: Using data from a large anonymised mental healthcare database, we identified all adult patients with serious mental illness (SMI) who had been prescribed a single antipsychotic or polypharmacy, for six or more months between 2007 and 2014. Multivariable Cox regression models were constructed, adjusting for sociodemographic, socioeconomic, clinical factors and smoking, to examine the association between APP use and the risk of death. RESULTS: We identified 10 945 adults with SMI who had been prescribed long-term antipsychotic monotherapy (76.9%) or APP (23.1%). Patients on long-term APP had a small elevated risk of mortality, which was significant in some but not all models. The adjusted hazard ratios for death from natural and unnatural causes associated with APP were 1.2 (0.9-1.4, P = 0.111) and 1.1 (0.7-1.9, P = 0.619) respectively. The strengths of the associations between APP and mortality outcomes were similar after further adjusting for % BNF antipsychotic dose (P = 0.031) or olanzapine equivalence (P = 0.088). CONCLUSION: The findings suggest that the effect of long-term APP on mortality is not clear-cut, with limited evidence to indicate an association, even after controlling for the effect of dose.

Closing the mortality gap for severe mental illness: are we going in the right direction?

In this editorial, we discuss a UK-based cohort study examining the mortality gap for people with schizophrenia and bipolar disorder from 2000 to 2014. There have been concerted efforts to improve physical and mental healthcare for this population in recent decades. Have these initiatives reduced mortality and 'closed the gap'?

Short-term Suicide Risk After Psychiatric Hospital Discharge.

IMPORTANCE: Although psychiatric inpatients are recognized to be at increased risk for suicide immediately after hospital discharge, little is known about the extent to which their short-term suicide risk varies across groups with major psychiatric disorders. OBJECTIVE: To describe the risk for suicide during the 90 days after hospital discharge for adults with first-listed diagnoses of depressive disorder, bipolar disorder, schizophrenia, substance use disorder, and other mental disorders in relation to inpatients with diagnoses of nonmental disorders and the general population. DESIGN, SETTING, AND PARTICIPANTS: This national retrospective longitudinal cohort included inpatients aged 18 to 64 years in the Medicaid program who were discharged with a first-listed diagnosis of a mental disorder (depressive disorder, bipolar disorder, schizophrenia, substance use disorder, and other mental disorder) and a 10% random sample of inpatients with diagnoses of nonmental disorders. The cohort included 770 643 adults in the mental disorder cohort, 1 090 551 adults in the nonmental disorder cohort, and 370 deaths from suicide from January 1, 2001, to December 31, 2007. Data were analyzed from March 5, 2015, to June 6, 2016. MAIN OUTCOMES AND MEASURES: Suicide rates per 100 000 person-years were determined for each study group during the 90 days after hospital discharge and the demographically matched US general population. Adjusted hazard ratios (ARHs) of short-term suicide after hospital discharge were also estimated by Cox proportional hazards regression models. Information on suicide as a cause of death was obtained from the National Death Index. RESULTS: In the overall population of 1 861 194 adults (27% men; 73% women; mean [SD] age, 35.4 [13.1] years), suicide rates for the cohorts with depressive disorder (235.1 per 100 000 person-years), bipolar disorder (216.0 per 100 000 person-years), schizophrenia (168.3 per 100 000 person-years), substance use disorder (116.5 per 100 000 person-years), and other mental disorders (160.4 per 100 000 person-years) were substantially higher than corresponding rates for the cohort with nonmental disorders (11.6 per 100 000 person-years) or the US general population (14.2 per 100 000 person-years). Among the cohort with mental disorders, AHRs of suicide were associated with inpatient diagnosis of depressive disorder (AHR, 2.0; 95% CI, 1.4-2.8; reference cohort, substance use disorder), an outpatient diagnosis of schizophrenia (AHR, 1.6; 95% CI, 1.1-2.2), an outpatient diagnosis of bipolar disorder (AHR, 1.6; 95% CI, 1.2-2.1), and an absence of any outpatient health care in the 6 months preceding hospital admission (AHR, 1.7; 95% CI, 1.2-2.5). CONCLUSIONS AND RELEVANCE: After psychiatric hospital discharge, adults with complex psychopathologic disorders with prominent depressive features, especially patients who are not tied into a system of health care, appear to have a particularly high short-term risk for suicide.

The effect of clozapine on premature mortality: an assessment of clinical monitoring and other potential confounders.

Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ≥ 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007-2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2-0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes.

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness.

BACKGROUND: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated. We aimed to assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations. METHODS: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations. RESULTS: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). CONCLUSIONS: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed.

Minnesota 10 by 10. Reducing morbidity and mortality in people with serious mental illnesses.

Persons with schizophrenia, schizoaffective disorder, and bipolar affective disorder in Minnesota are dying much younger than their age- and sex-matched cohorts. A new initiative, MN 10 By 10, is designed to engage key constituencies in addressing modifiable risk factors in order to lengthen these individuals' lives.

Cost effectiveness of adjunctive quetiapine fumarate extended-release tablets with mood stabilizers in the maintenance treatment of bipolar I disorder.

BACKGROUND: Bipolar I disorder (BPD I) is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. However, few studies have investigated the cost effectiveness of maintenance treatment options for BPD I. OBJECTIVE: To determine the cost effectiveness of maintenance treatment with quetiapine fumarate extended-release (XR) tablets in combination with mood stabilizers (lithium or divalproex) in comparison with the following treatments: placebo in combination with lithium or divalproex; no maintenance treatment; lithium monotherapy; lamotrigine monotherapy; olanzapine monotherapy; and aripiprazole monotherapy. METHODS: The analysis was conducted from the societal and payer perspectives in the US, using a Markov model. The model simulated a cohort of 1000 stabilized BPD I patients and estimated the quarterly risk in three health states: euthymia, mania and depression. Efficacy data were derived from two randomized, double-blind trials comparing quetiapine + lithium/divalproex with placebo + lithium/divalproex for up to 2 years, as well as other published literature. Resource data were extracted from published literature. Drug costs, hospitalizations and physician visits were among the direct costs. Indirect costs included absenteeism, and mortality rates included suicide. Benefits and costs were discounted at 3% and the price reference year was 2009. Endpoints included number of acute mood episodes, hospitalizations due to an acute mood event and costs per QALY. Probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty in the model inputs. RESULTS: Treatment with quetiapine XR + lithium/divalproex was associated with reductions in acute mania (46%), acute depression (41%) and related hospitalizations (44%) compared with placebo + lithium/divalproex, and similar reductions in events were observed relative to lithium monotherapy. In the base-case analysis from the payer perspective, the discounted incremental cost per QALY for quetiapine XR + lithium/divalproex compared with placebo + lithium/divalproex was $US22 959, and compared with lithium monotherapy was $US100 235, while all other comparators were dominated. PSA showed these results to be robust to select assumptions. CONCLUSIONS: Quetiapine XR + lithium/divalproex may be a cost-effective maintenance treatment option for patients with BPD I.

Diagnostic features, prevalence, and impact of bipolar disorder.

Bipolar disorder shares depressive symptoms with unipolar major depressive disorder but is defined by episodes of mania or hypomania. Bipolar disorder in its broadest sense has a community lifetime prevalence of 4% and is a severely impairing illness that impacts several aspects of patients' lives. Race, ethnicity, and gender have no effect on prevalence rates, but women are more likely to experience rapid cycling, mixed states, depressive episodes, and bipolar II disorder than men. Patients with bipolar disorder have high rates of disability and higher rates of mortality than individuals without bipolar disorder. Natural causes such as cardiovascular disease and diabetes, as well as suicide and other "unnatural" causes are key contributors to the high mortality rate. The costs associated with bipolar disorder include not only the direct costs of treatment, but also the much greater indirect costs of decreased productivity, excess unemployment, and excess mortality.

Manic/hypomanic symptom burden and cardiovascular mortality in bipolar disorder.

OBJECTIVES: To compare the risk for cardiovascular mortality between bipolar I and bipolar II subtypes and determine correlates of cardiovascular mortality. Bipolar disorder conveys an increased risk of cardiovascular mortality. METHODS: Participants with major affective disorders were recruited for the National Institute of Mental Health Collaborative Depression Study and followed prospectively for up to 25 years. A total of 435 participants met the diagnostic criteria for bipolar I (n = 288) or bipolar II (n = 147) disorder based on Research Diagnostic Criteria at intake and measures of psychiatric symptoms during follow-up. Diagnostic subtypes were contrasted by cardiovascular mortality risk using Cox proportional hazards regression. Affective symptom burden (the proportion of time with clinically significant manic/hypomanic or depressive symptoms) and treatment exposure were additionally included in the models. RESULTS: Thirty-three participants died from cardiovascular causes. Participants with bipolar I disorder had more than double the cardiovascular mortality risk of those with bipolar II disorder, after controlling for age and gender (hazard ratio = 2.35, 95% Confidence Interval = 1.04-5.33; p = .04). The observed difference in cardiovascular mortality between these subtypes was at least partially confounded by the burden of clinically significant manic/hypomanic symptoms which predicted cardiovascular mortality independent of diagnosis, treatment exposure, age, gender, and cardiovascular risk factors at intake. Selective serotonin uptake inhibitors seemed protective although they were introduced late in follow-up. Depressive symptom burden was not related to cardiovascular mortality. CONCLUSIONS: Participants with bipolar I disorder may face a greater risk of cardiovascular mortality than those with bipolar II disorder. This difference in cardiovascular mortality risk may reflect manic/hypomanic symptom burden.

Sex and ethnic differences among South Tirolean suicides: a psychological autopsy study.

OBJECTIVE: The aim of the research is to study whether any differences exist in the rates and characteristics of suicide by ethnicity and sex in South Tirol, Italy. METHODS: Psychological autopsy interviews were conducted for suicides who died between March 1997 and July 2006. RESULTS: 332 individuals belonging to the three major South Tirolean ethnic groups (Germans, Italians, Ladins [Ladin is a Rhaeto-Romance language related to the Venetian and Swiss Romansh languages]) died by suicide. Around 23% of the victims had experienced suicidal behaviour among family members, and more than 31% of them had experienced trauma during their childhood. Germans were 1.37 times more at risk to commit suicide than Italians (95% CI: 1.04/1.80; z=2.26, p<.05). 69% of the suicides had attended school for less than 8 years: Germans (OR=4.62; 95% CI: 2.52/8.47; p<.001) and Ladins (OR=11.24; 95% CI: 2.99/42.30; p<.001) were more likely to have lower education than Italians. There were several differences by ethnicity and sex but no sex-by-ethnicity interactions. CONCLUSIONS: The study indicated that suicide, an alarming health and social problem in South Tirol, may require different preventive interventions for men and women and for those of different ethnicities.

Do risk factors for suicidal behavior differ by affective disorder polarity?

BACKGROUND: Suicide is a leading cause of death and has been strongly associated with affective disorders. The influence of affective disorder polarity on subsequent suicide attempts or completions and any differential effect of suicide risk factors by polarity were assessed in a prospective cohort. METHOD: Participants with major affective disorders in the National Institute of Mental Health (NIMH) Collaborative Depression Study (CDS) were followed prospectively for up to 25 years. A total of 909 participants meeting prospective diagnostic criteria for major depressive and bipolar disorders were followed through 4204 mood cycles. Suicidal behavior was defined as suicide attempts or completions. Mixed-effects, grouped-time survival analysis assessed risk of suicidal behavior and differential effects of risk factors for suicidal behavior by polarity. In addition to polarity, the main effects of age, gender, hopelessness, married status, prior suicide attempts and active substance abuse were modeled, with mood cycle as the unit of analysis. RESULTS: After controlling for age of onset, there were no differences in prior suicide attempts by polarity although bipolar participants had more prior severe attempts. During follow-up, 40 cycles ended in suicide and 384 cycles contained at least one suicide attempt. Age, hopelessness and active substance abuse but not polarity predicted suicidal behavior. The effects of risk factors did not differ by polarity. CONCLUSIONS: Bipolarity does not independently influence risk of suicidal behavior or alter the influence of well-established suicide risk factors within affective disorders. Suicide risk assessment strategies may continue to appraise these common risk factors without regard to mood polarity.

Mortality among first-admission patients with psychosis.

OBJECTIVE: This study compared 5- and 10-year survival and absolute and relative mortality rates among first-admission patients with 1 of 4 psychotic disorders: schizophrenia/schizoaffective disorder, bipolar disorder, major depression, and other nonorganic psychoses. METHOD: The authors conducted a prospective 10-year follow-up of subjects first admitted with a diagnosis of nonorganic psychosis to any of 12 hospitals in Suffolk County, New York, during the period 1989 to 1995. Information on their death status since study entry was ascertained from the Social Security Death Index and the National Death Index. Survival analyses were conducted using the Kaplan-Meier product-limit estimator. RESULTS: There were no significant differences in survival rates among the 4 diagnostic groups at 5-year (range, 96.3%-97.8%) or 10-year (range, 90.2%-97.8%) follow-up. Absolute mortality over the study period ranged from 2.8% of bipolars to 6.7% of those with major depression. About 60% of deaths among schizophrenic/schizoaffective subjects were due to unnatural causes, whereas for the other 3 groups, deaths were more evenly split between natural and unnatural causes. Suicides comprised most deaths from unnatural causes, most of which occurred during the 2- to 5-year follow-up period. Deaths due to natural causes tended to be related to lifestyle factors. CONCLUSIONS: First-admission patients with psychosis experience similar patterns of mortality risk over the first 10 years after index admission regardless of underlying diagnosis. Causes of death (both natural and unnatural) were potentially preventable with more intensive medical and psychiatric follow-up and intervention. Many deaths from unnatural causes occurred during or shortly after discharge from an inpatient or residential treatment setting, highlighting this period as one needing close scrutiny by treating clinicians.

Metabolism, lifestyle and bipolar affective disorder.

Lifestyle, illness and treatment factors in people with bipolar disorder (BD) may confer additional risk of morbidity and mortality to the increasing rates of obesity, metabolic syndrome, diabetes mellitus and cardiovascular mortality in the general population.The aim of this review is to examine whether the risk of obesity and related morbidity and mortality are raised in BD, and possible contributory effects of lifestyle, illness and treatment factors to this risk.Systematic search of Medline and Cochrane Collaboration for relevant studies followed by a critical review of literature was carried out.Mortality from cardiovascular causes and pulmonary embolism (standardized mortality ratio approximately 2.0), and morbidity from obesity and type 2 diabetes mellitus may be increased in BD compared to the general population. Reduced exercise and poor diet, frequent depressive episodes, comorbidity with substance misuse and poor quality general medical care contribute to the additional risk of these medical problems in people with BD. There is no evidence that patients with BD are more sensitive than other patients to weight gain and medical problems associated with long-term use of psychotropic medication; in fact long-term treatment with lithium, antipsychotics and tricyclic antidepressants may reduce overall mortality. Psychiatrists, general practitioners and other health professionals should work together to systematically assess and manage weight gain and related medical problems to reduce the morbidity and mortality associated with obesity in BD. There is insufficient evidence to associate any of these factors with specific drug treatments. More research is required to understand how BD changes the risk for physical health comorbidity.