Mortality trends in external causes of death in people with mental health disorders in Sweden, 1987-2010.

AIM: We investigated mortality from external causes in Swedish people who had been hospitalised with a severe mental disorder. METHODS: Hospitalisations in people aged 15 years or older admitted to hospital with a main diagnosis of schizophrenia, bipolar mood disorder or unipolar mood disorder between 1987 and 2010 were linked to their causes of death. RESULTS: The mortality rate from all external causes was 20-fold higher in those with unipolar mood disorder, 15-fold higher in those with bipolar disorder and 12-fold higher in those with schizophrenia than in the general population. Over the study periods, the mortality rate declined more for people with unipolar mood disorder (-35%) and schizophrenia (-29%) than the total population (-25%) and those with bipolar mood disorder (-15%). The suicide rate declined most for those with unipolar mood disorder and schizophrenia (-42% for both) and less for the general population (-37%) and those with bipolar mood disorder (-21%). For external causes other than suicide, the mortality rate declined in the general population (-17%) but increased in people with schizophrenia (14%), bipolar mood disorder (30%) and unipolar mood disorder (52%). CONCLUSIONS: People with mental disorders have high but declining excess mortality from suicide. Mortality from other external causes has increased, as has the gap in mortality rates between psychiatric patients and the general population.

Risk of neurological, eye and ear disease in offspring to parents with schizophrenia or depression compared with offspring to healthy parents.

BACKGROUND: Neurological, visual and hearing deviations have been observed in the offspring of parents with schizophrenia. This study test whether children to parents hospitalized with schizophrenia have increased the likelihood of childhood neurological disorder. METHODS: Among all parents in Sweden born 1950-1985 and with offspring born 1968-2002: 7107 children with a parent hospitalized for schizophrenia were compared to 172 982 children with no parents hospitalized for schizophrenia or major depression, as well as to 32 494 children with a parent hospitalized for major depression as a control population with another severe psychiatric outcome. We estimated relative risks (RR) and two-sided 95% confidence intervals calculated from Poisson regression. RESULTS: Children to parents with schizophrenia were more likely than controls to have been hospitalized before the age of 10 with a diagnosis of cerebral palsy, RR = 1.76 (95% CI: 1.15-2.69); epilepsy, RR = 1.78 (95% CI: 1.33-2.40), combined neurological disease, RR = 1.33 (95% CI: 1.11-1.60) and certain diseases of the eye, RR = 1.92 (95% CI: 1.17-3.15) and ear, RR = 1.18 (95% CI: 1.05-1.32). Similar disease-risk-pattern was found for children to parents hospitalized with a diagnosis of major depression. A specific risk increase for strabismus RR = 1.21 (95%CI: 1.05-1.40) was found for off-spring with parental depression. CONCLUSIONS: Compared with children to healthy parents, children to parents with schizophrenia have increased risk of a variety of neurological disorders as well as visual and hearing disorders at an early age. The risk increase was not specific to schizophrenia but was also seen in children to parents with a diagnosis of major depression.

Lithium treatment and cancer incidence in bipolar disorder.

OBJECTIVES: To investigate whether there is an increased risk of cancer associated with lithium treatment in patients with bipolar disorder compared to the general population. METHODS: A nationwide Swedish register study of incidence rate ratios (IRRs) of total cancer and site-specific cancer in the 50-84-year age range was carried out in patients with bipolar disorder (n = 5,442) with and without lithium treatment from July 2005 to December 2009 compared to the general population using linked information from The Swedish Cancer Register, The National Patient Register, and The Drug Prescription Register. RESULTS: The overall cancer risk was not increased in patients with bipolar disorder. There was no difference in risk of unspecified cancer, neither in patients with lithium treatment compared to the general population [IRR = 1.04, 95% confidence interval (CI): 0.89-1.23] nor in patients with bipolar disorder without lithium treatment compared to the general population (IRR = 1.03, 95% CI: 0.89-1.19). The cancer risk was significantly increased in patients with bipolar disorder without lithium treatment in the digestive organs (IRR = 1.47, 95% CI: 1.12-1.93), in the respiratory system and intrathoracic organs (IRR = 1.72, 95% CI: 1.11-2.66), and in the endocrine glands and related structures (IRR = 2.60, 95% CI: 1.24-5.47), but in patients with bipolar disorder with lithium treatment, there was no significantly increased cancer risk compared to the general population. CONCLUSIONS: Bipolar disorder was not associated with increased cancer incidence and neither was lithium treatment in these patients. Specifically, there was an increased risk of respiratory, gastrointestinal, and endocrine cancer in patients with bipolar disorder without lithium treatment.

Mortality trends in cardiovascular causes in schizophrenia, bipolar and unipolar mood disorder in Sweden 1987-2010.

INTRODUCTION: People with severe mental illness have increased risk for premature mortality and thus a shorter life expectancy. Relative death rates are used to show the excess mortality among patients with mental health disorder but cannot be used for the comparisons by country, region and time. METHODS: A population-based register study including all Swedish patients in adult psychiatry admitted to hospital with a main diagnosis of schizophrenia, bipolar or unipolar mood disorder in 1987-2010 (614 035 person-years). Mortality rates adjusted for age, sex and period were calculated using direct standardization methods with the 2010 Swedish population as standard. Data on all residents aged 15 years or older were used as the comparison group. RESULTS: Patients with severe mental health disorders had a 3-fold mortality compared to general population. All-cause mortality decreased by 9% for people with bipolar mood disorder and by 26-27% for people with schizophrenia or unipolar mood disorder, while the decline in the general population was 30%. Also mortality from diseases of the circulatory system declined less for people with severe mental disorder (-35% to - 42%) than for general population (-49%). The pattern was similar for other cardiovascular deaths excluding cerebrovascular deaths for which the rate declined among people with schizophrenia (-30%) and unipolar mood disorder (-41%), unlike for people with bipolar mood disorder (-3%). CONCLUSIONS: People with mental health disorder have still elevated mortality. The mortality declined faster for general population than for psychiatric patients. More detailed analysis is needed to reveal causes-of-death with largest possibilities for improvement.

Excess mortality among people in homelessness with substance use disorders: a Swedish cohort study.

BACKGROUND: People in homelessness have an increased risk of substance use disorders (SUDs) and poor health outcomes. This cohort study aimed to investigate the association between homelessness and mortality in people with SUDs, adjusting for age, sex, narcotic use, intravenous drug use and inpatient care for SUDs. METHODS: Data from the Swedish National Addiction Care Quality Register in the Stockholm region were used to analyse mortality risk in people with SUDs (n=8397), including 637 in homelessness, 1135 in precarious housing and 6625 in stable housing, at baseline. HRs and CIs were calculated using Cox regression. RESULTS: Mortality was increased for people in homelessness (HR 2.30; 95% CI 1.70 to 3.12) and precarious housing (HR 1.23; 95% CI 0.86 to 1.75) compared with those in stable housing. The association between homelessness and mortality decreased (HR 1.27; 95% CI 0.91 to 1.78) after adjusting for narcotic use (HR 1.28; 95% CI 1.00 to 1.63), intravenous drug use (HR 1.98; 95% CI 1.52 to 2.58) and inpatient care for SUDs (HR 1.96; 95% CI 1.57 to 2.45). Standardised mortality ratios (SMRs) showed that mortality among people in homelessness with SUDs was 13.6 times higher than the general population (SMR=13.6; 95% CI 10.2 to 17.9), and 3.7 times higher in people in stable housing with SUDs (SMR=3.7; 95% CI 3.2 to 4.1). CONCLUSION: Homelessness increased mortality, but the risk decreased after adjusting for narcotic use, intravenous drug use and inpatient care for SUDs. Interventions are needed to reduce excess mortality among people in homelessness with SUDs.

Outcomes of psychiatric interviews and self-rated symptom scales in people on sick leave for common mental disorders: an observational study.

OBJECTIVES: To investigate the correspondence between diagnoses on sick leave certificates and diagnoses made in structured psychiatric interviews. Secondary aims were to investigate length of sick leave by diagnoses on sick leave certificates, diagnoses made in structured interviews and symptom severity. DESIGN: Observational study consisting of a secondary analysis of data from a randomised controlled trial and an observational study. SETTING: The regions of Stockholm and Västra Götaland, Sweden. PARTICIPANTS: 480 people on sick leave for common mental disorders. INTERVENTIONS: Participants were examined with structured psychiatric interviews and self-rated symptom severity scales. OUTCOME MEASURES: (1) Sick leave certificate diagnoses, (2) diagnoses from the Mini International Neuropsychiatric Interview and the Self-rated Stress-Induced Exhaustion Disorder (SED) Instrument (s-ED), (3) symptom severity (Montgomery-Asberg Depression Rating Scale-self-rating version and the Karolinska Exhaustion Disorder Scale) and (4) number of sick leave days. RESULTS: There was little correspondence between diagnoses on sick leave certificates and diagnoses made in structured psychiatric interviews. Many participants on sick leave for SED, anxiety disorder or depression fulfilled criteria for other mental disorders. Most on sick leave for SED (76%) and anxiety disorder (67%) had depression (p=0.041). Length of sick leave did not differ by certificate diagnoses. Participants with SED (s-ED) had longer sick leave than participants without SED (144 vs 84 days; 1.72 (1.37-2.16); p<0.001). More severe symptoms were associated with longer sick leave. CONCLUSION: Diagnoses on sick leave certificates did not reflect the complex and overlapping nature of the diagnoses found in the structured psychiatric interviews. This finding is relevant to the interpretation of information from health data registers, including studies and guidelines based on these data. A result of clinical interest was that more severe symptoms predicted long-term sick leave better than actual diagnoses.

Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: population based cohort study of long term incidence and mortality.

OBJECTIVE: To determine factors influencing long term risks for acquiring or dying from invasive cervical or vaginal cancer in women previously treated for cervical intraepithelial neoplasia grade 3 (CIN3). DESIGN: Population based cohort study conducted in 1958-2008, followed up until 2009 in the Swedish Cancer Registry and Swedish Cause of Death Register, linked to the Swedish Population Register. Standardised incidence and mortality ratios were calculated for the risk of acquiring or dying from vaginal or cervical cancer, with the general female population in Sweden as reference. Relative risks in multivariable regression models were also calculated, adjusting for follow-up duration, treatment period, and age at CIN3 treatment or attained age. SETTING: Entire female population of Sweden. PARTICIPANTS: 150,883 women in Sweden diagnosed and treated with CIN3 and followed up for invasive cervical or vaginal cancer, and related mortality. The cohort comprised 3,148,222 woman years. MAIN OUTCOME MEASURES: Standardised incidence and mortality ratios, stratified by period for treatment. Relative standardised incidence ratios and standardised mortality ratios for age at acquiring or dying from cervical or vaginal cancer (attained age), adjusted for preset variables. RESULTS: Women previously diagnosed with CIN3 had an increased risk of dying from invasive cervical or vaginal cancer, compared with the general female population (standardised mortality ratio 2.35, 95% confidence interval 2.11 to 2.61). After age 60 years, these women had an accelerated increased risk of acquiring invasive cancer; a similar steep increase in mortality risk was seen after age 70. Regression analyses indicated that the increase in risk over time is highly attributable to ageing. CONCLUSIONS: Women previously treated for CIN3 are at increased risk of developing and dying from cervical or vaginal cancer, compared with the general female population. The risk accelerates above age 60 years, suggesting a need for lifelong surveillance of these women.

Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden.

OBJECTIVE: To estimate the cardiovascular mortality among persons with bipolar disorder in Sweden compared to the general population. DESIGN: Population register-based cohort study with a 20-year follow-up. SETTING: Sweden. PARTICIPANTS: The entire population of Sweden (n=10.6 million) of whom 17 101 persons were diagnosed with bipolar disorder between 1987 and 2006. MAIN OUTCOME MEASURES: Mortality rate ratios (MRR), excess mortality (excess deaths), cardiovascular disorder (CVD) and specifically cerebrovascular disease, coronary heart disease, acute myocardial infarction, sudden cardiac deaths and hospital admission rate ratio (ARR). RESULTS: Persons with bipolar disorder died of CVD approximately 10 years earlier than the general population. One third (38%) of all deaths in persons with bipolar disorder were caused by CVD and almost half (44%) by other somatic diseases, whereas suicide and other external causes accounted for less than a fifth of all deaths (18%). Excess mortality of both CVD (n=824) and other somatic diseases (n=988) was higher than that of suicide and other external causes (n=675 deaths). MRRs for cerebrovascular disease, coronary heart disease and acute myocardial infarction were twice as high in persons with bipolar disorder compared to the general population. Despite the increased mortality of CVD, hospital admissions (ARR) for CVD treatment were only slightly increased in persons with bipolar disorder when compared to the general population. CONCLUSIONS: The increased cardiovascular mortality in persons with bipolar disorder calls for renewed efforts to prevent and treat somatic diseases in this group. Specifically, our findings further imply that it would be critical to ensure that persons with bipolar disorder receive the same quality care for CVD as persons without bipolar disorder.

Excess mortality, causes of death and life expectancy in 270,770 patients with recent onset of mental disorders in Denmark, Finland and Sweden.

BACKGROUND: Excess mortality among patients with severe mental disorders has not previously been investigated in detail in large complete national populations. OBJECTIVE: To investigate the excess mortality in different diagnostic categories due to suicide and other external causes of death, and due to specific causes in connection with diseases and medical conditions. METHODS: In longitudinal national psychiatric case registers from Denmark, Finland, and Sweden, a cohort of 270,770 recent-onset patients, who at least once during the period 2000 to 2006 were admitted due to a psychiatric disorder, were followed until death or the end of 2006. They were followed for 912,279 person years, and 28,088 deaths were analyzed. Life expectancy and standardized cause-specific mortality rates were estimated in each diagnostic group in all three countries. RESULTS: The life expectancy was generally approximately 15 years shorter for women and 20 years shorter for men, compared to the general population. Mortality due to diseases and medical conditions was increased two- to three-fold, while excess mortality from external causes ranged from three- to 77-fold. Mortality due to diseases and medical conditions was generally lowest in patients with affective disorders and highest in patients with substance abuse and personality disorders, while mortality due to suicide was highest in patients with affective disorders and personality disorders, and mortality due to other external causes was highest in patients with substance abuse. CONCLUSIONS: These alarming figures call for action in order to prevent the high mortality.

Life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in the Nordic countries.

OBJECTIVE: Excess mortality from diseases and medical conditions (natural death) in persons with psychiatric disorders has been extensively reported. Even in the Nordic countries with well-developed welfare systems, register based studies find evidence of an excess mortality. In recent years, cardiac mortality and death by diseases of the circulatory system has seen a decline in all the Nordic countries, but a recent paper indicates that women and men in Denmark, Finland, and Sweden, who had been hospitalised for a psychotic disorder, had a two to three-fold increased risk of dying from a cardiovascular disease. The aim of this study was to compare the mortality by diseases of the circulatory system among patients with bipolar disorder or schizophrenia in the three Nordic countries Denmark, Sweden, and Finland. Furthermore, the aim was to examine and compare life expectancy among these patients. Cause specific Standardized Mortality Rates (SMRs) were calculated for each specific subgroup of mortality. Life expectancy was calculated using Wiesler's method. RESULTS: The SMR for bipolar disorder for diseases of the circulatory system was approximately 2 in all countries and both sexes. SMR was slightly higher for people with schizophrenia for both genders and in all countries, except for men in Denmark. Overall life expectancy was much lower among persons with bipolar disorder or schizophrenia, with life expectancy being from 11 to 20 years shorter. CONCLUSION: Our data show that persons in the Nordic countries with schizophrenia or bipolar disorder have a substantially reduced life expectancy. An evaluation of the reasons for these increased mortality rates should be prioritized when planning healthcare in the coming years.

The incidence of narcolepsy in Europe: before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns.

BACKGROUND: In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification. METHODS: We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000-2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom. RESULTS: Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90-0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women>men) and around 60 years of age. In the age group 5-19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1-3.1) in Denmark, 6.4 (95% CI: 4.2-9.7) in Finland and 7.5 (95% CI: 5.2-10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time. CONCLUSIONS: The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.

Risk of presentation to hospital with epileptic seizures after vaccination with monovalent AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix): self controlled case series study.

OBJECTIVE: To assess the risk of epileptic seizures in people with and without epilepsy after vaccination with a monovalent AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix; Glaxo SmithKline, Sweden). DESIGN: Register based self controlled case series. SETTING: Three Swedish counties (source population 750,000). PARTICIPANTS: 373,398 people (age 0-106, median 41.2) who were vaccinated. Vaccinated people with epileptic seizures, diagnosed as inpatients or outpatients, at any time from 90 days before until 90 days after any dose of vaccine. MAIN OUTCOME MEASURES: Endpoints were admission to hospital or outpatient hospital care with epileptic seizures as the main diagnosis. The effect estimate of relative incidence was calculated as the incidence of epileptic seizures in period after exposure relative to the incidence of epileptic seizures in two control periods, one before and one after vaccination. RESULTS: 859 people experienced epileptic seizures during the study period. There was no increased risk of seizures in people with previously diagnosed epilepsy (relative incidence 1.01, 95% confidence interval 0.74 to 1.39) and a non-significant decrease in risk for people without epilepsy (0.67, 0.27 to 1.65) during the day 1-7 risk period (where day 1 is the day of vaccination). In a second risk period (day 8-30), there was a non-significant increased risk of seizures in people without epilepsy (1.11, 0.73 to 1.70) but no increase in risk for those with epilepsy (1.00, 0.83 to 1.21). CONCLUSIONS: This study found no evidence of an increase in risk of presentation to hospital with epileptic seizures after vaccination with a monovalent AS03 adjuvanted pandemic H1N1 influenza vaccine.