Charlotte Björkenstam

Antipsychotic Treatment and Mortality in Schizophrenia

BACKGROUND It is generally believed that long-term use of antipsychotics increases mortality and, especially, the risk of cardiovascular death. However, there are no solid data to substantiate this view. METHODS We identified all individuals in Sweden with schizophrenia diagnoses before year 2006 (N = 21 492), aged 17-65 years, and persons with first-episode schizophrenia during the follow-up 2006-2010 (N = 1230). Patient information was prospectively collected through nationwide registers. Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010. RESULTS Compared with age- and gender-matched controls from the general population (N = 214920), the highest overall mortality was observed among patients with no antipsychotic exposure (hazard ratio [HR] = 6.3, 95% CI: 5.5-7.3), ie, 0.0 defined daily dose (DDD)/day, followed by high exposure (>1.5 DDD/day) group (HR = 5.7, 5.2-6.2), low exposure (<0.5 DDD/day) group (HR = 4.1, 3.6-4.6), and moderate exposure (0.5-1.5 DDD/day) group (HR = 4.0, 3.7-4.4). High exposure (HR = 8.5, 7.3-9.8) and no exposure (HR = 7.6, 5.8-9.9) were associated with higher cardiovascular mortality than either low exposure (HR = 4.7, 3.7-6.0) or moderate exposure (HR = 5.6, 4.8-6.6). The highest excess overall mortality was observed among first-episode patients with no antipsychotic use (HR = 9.9, 5.9-16.6). CONCLUSIONS Among patients with schizophrenia, the cumulative antipsychotic exposure displays a U-shaped curve for overall mortality, revealing the highest risk of death among those patients with no antipsychotic use. These results indicate that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than antipsychotic treatment when used in adequate dosages.

School grades, parental education and suicide—a national register-based cohort study

Background To investigate whether school performance is a risk factor for suicide death later in life and, if so, to what extent this is explained by intergenerational effects of parental education. Methods This population-based cohort study comprises national birth cohorts between 1972 and 1981 in Sweden. We followed 898 342 students, graduating between 1988 and 1997 from the 9 years of compulsory school, equivalent to junior high school, until 31 December 2006, generating 11 148 758 person-years and 1490 suicides. Final school grades, in six categories, and risk of suicide were analysed with Poisson regression. Results The incidence rate ratio (RR) for suicide death for students with the lowest grades was 4.57 (95% CI 2.82 to 7.40) for men and 2.67 (1.42 to 5.01) for women compared to those with highest grades after adjustment for a number of sociodemographic and parental morbidity variables, such as year of graduation, parental education, lone parenthood, household receiving social welfare or disability pension, place of schooling, adoption, maternal age and parents mental illness. Students with grades in the middle categories had RRs in between. These relationships were not modified by parental education. Conclusions The strong association between low school grades and suicide in youth and young adulthood emphasises the importance of both primary and secondary prevention in schools.

Suicide or undetermined intent? A register-based study of signs of misclassification.

BackgroundSeveral studies have concluded that some deaths classified as undetermined intent are in fact suicides, and it is common in suicide research in Europe to include these deaths. Our aim was to investigate if information on background variables would be helpful in assessing if deaths classified as undetermined intent should be included in the analyses of suicides.MethodsWe performed a register study of 31,883 deaths classified as suicides and 9,196 deaths classified as undetermined intent in Sweden from 1987 to 2011. We compared suicide deaths with deaths classified as undetermined intent with regard to different background variables such as sex, age, country of birth, marital status, prior inpatient care for self-inflicted harm, alcohol and drug abuse, psychiatric inpatient care, and use of psychotropics. We also performed a multivariate analysis with logistic regression.ResultsOur results showed differences in most studied background factors. Higher education was more common in suicides; hospitalization for self-inflicted harm was more common among female suicides as was prior psychiatric inpatient care. Deaths in foreign-born men were classified as undetermined intent in a higher degree and hospitalization for substance abuse was more common in undetermined intents of both sexes. Roughly 50% of both suicide and deaths classified as undetermined intent had a filled prescription of psychotropics during their last six months. Our multivariate analysis showed male deaths to more likely be classified as suicide than female: OR: 1.13 (1.07-1.18). The probability of a death being classified as suicide was also increased for individuals aged 15–24, being born in Sweden, individuals who were married, and for deaths after 1987–1992.ConclusionBy analyzing Sweden’s unique high-validity population-based register data, we found several differences in background variables between deaths classified as suicide and deaths classified as undetermined intent. However, we were not able to clearly distinguish these two death manners. For future research we suggest, separate analyses of the two different manners of death.

Suicide in first episode psychosis : A nationwide cohort study

BACKGROUND Relatively little is known about suicide in diagnostic subtypes of first episode psychosis (FEP). Our aim was to assess suicide rates and potential risk factors for suicide in FEP. METHODS This is a national register-based cohort study of patients born in 1973-1978 in Sweden and who were hospitalized with a FEP between ages 15 and 30years (n=2819). The patients were followed from date of discharge until death, emigration, or 31st of December 2008. The suicide rates for six diagnostic subtypes of FEP were calculated. Suicide incidence rate ratios (IRRs) were calculated to evaluate the association between suicide and psychiatric, familial, social, and demographic factors. RESULTS In total 121 patients died by suicide. The overall suicide rate was 4.3 (95% confidence interval [CI] 3.5-5.0) per 1000person-years. The highest suicide rates were found in depressive disorder with psychotic symptoms and in delusional disorder. In an adjusted model, the strongest risk factors for suicide were self-harm (IRR 2.7, CI 1.7-4.4) or a conviction for violent crime (IRR 2.0, CI 1.3-3.2). Also having a first-degree relative with a schizophrenia/bipolar diagnosis (IRR 2.1, CI 1.2-3.6) or substance use disorder (IRR 2.0, CI 1.2-3.2) were significant risk factors for suicide. CONCLUSIONS Impulsive behavior such as self-harm as well as having a family history of severe mental disorder or substance use are important risk factors for suicide in FEP.

Sexual Orientation and All-Cause Mortality Among US Adults Aged 18 to 59 Years, 2001–2011

To determine whether sexual minorities have an earlier mortality than do heterosexuals, we investigated associations between sexual orientation assessed in the 2001 to 2010 National Health and Nutrition Examination Surveys (NHANES) and mortality in the 2011 NHANES-linked mortality file. Mortality follow-up time averaged 69.6 months after NHANES. By 2011, 338 individuals had died. Sexual minorities evidenced greater all-cause mortality than did heterosexuals after adjusting for demographic confounding. These effects generally disappeared with further adjustment for NHANES-detected health and behavioral differences.

Excess cause-specific mortality in in-patient-treated individuals with personality disorder: 25-year nationwide population-based study

BACKGROUND Although personality disorders are associated with increased overall mortality, less is known about cause of death and personality type. AIMS To determine causes of mortality in ICD personality disorders. METHOD Based on data from Swedish nationwide registers, individuals admitted to hospital with a primary diagnosis of personality disorder between 1987 and 2011 were followed with respect to mortality until 31 December 2011. Standardised mortality ratios (SMRs) with 95% confidence intervals and underlying causes of death were calculated. RESULTS All-cause SMRs were increased, overall and in all clusters, for natural as well as unnatural causes of death. The overall SMR was 6.1 in women and 5.0 in men, as high as previously reported for anorexia nervosa, with higher rates in cluster B and mixed/other personality disorders. The SMR for suicide was 34.5 in women and 16.0 in men for cluster B disorders. Somatic and psychiatric comorbidity increased SMRs. CONCLUSIONS The SMR was substantially increased for all personality disorder clusters. Thus, there was an increased premature mortality risk for all personality disorders, irrespective of category.

Psychiatric Diagnoses, Medication and Risk for Disability Pension in Multiple Sclerosis Patients; a Population- Based Register Study

Background Psychiatric comorbidity is common among multiple sclerosis (MS) patients. The majority of MS patients of working ages are on disability pension. The aims of this study were to chart the prevalences of psychiatric diagnoses and medications among MS patients of working ages, and to investigate their association with the risk for future disability pension. Methods This nationwide, population-based prospective cohort study includes 10,750 MS patients and 5,553,141 non-MS individuals who in 2005 were aged 17–64 years. Psychiatric diagnoses and medications were identified using nationwide registers. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated adjusting for socio-demographics. Furthermore, a survival analysis with five-year follow-up was performed among the 4,571 MS patients not on disability pension in 2005, with psychiatric diagnoses and medication as risk factors, and disability pension as the outcome. Results Among MS patients, 35% had been prescribed psychiatric medication compared to 10% of non-MS individuals, adjusted OR 3.72 (95% CI 3.57 to 3.88). Ten percent of MS patients had received a psychiatric diagnosis, compared to 5.7% of non-MS individuals, OR 1.82 (95% CI 1.71 to 1.94). Serotonin reuptake inhibitors (SSRIs), were the most commonly prescribed drugs (17%) among MS patients, while depression (4.8%) was the most common psychiatric diagnosis. In the survival analysis, MS patients with any psychiatric diagnosis had a hazard ratio (HR) of 1.83 (95% CI 1.53 to 2.18) for disability pension compared to other MS patients. MS patients with any psychiatric drug prescription had a HR for disability pension of 2.09 (95% CI 1.84 to 2.33). Conclusion Psychiatric diagnoses and medications are common among MS patients and adversely affect risk for disability pension. This highlights the importance of correct diagnosis and management of psychiatric comorbidity, in a clinical as well as in a societal perspective.

Co-morbidities increase the risk of disability pension among MS patients: a population-based nationwide cohort study

BackgroundMultiple sclerosis (MS) is a chronic and often disabling disease. In 2005, 62% of the MS patients in Sweden aged 16–65 years were on disability pension. The objective of this study is to investigate whether the presence of common co-morbidities increase MS patients’ risk for disability pension.MethodsThis population-based cohort study included 4 519 MS patients and 4 972 174 non-MS patients who in 2005 were aged 17–64 years, lived in Sweden, and were not on disability pension. Patients with MS were identified in the nationwide in- and outpatient registers, while four different registers were used to construct three sets of measures of musculoskeletal, mental, and cardiovascular disorders. Time-dependent proportional hazard models with a five-year follow up were performed, adjusting for socio-demographic factors.ResultsAll studied disorders were elevated among MS patients, regardless of type of measure used. MS patients with mental disorders had a higher risk for disability pension than MS patients with no such co-morbidities. Moreover, mental disorders had a synergistic influence on MS patients’ risk for disability pension. These findings were also confirmed when conducting sensitivity analyses. Musculoskeletal disorders appeared to increase MS patients’ risk for disability pension. The results with regard to musculoskeletal disorders’ synergistic influence on disability pension were however inconclusive. Cardiovascular co-morbidity had no significant influence on MS-patients’ risk for disability pension.ConclusionsCo-morbidities, especially mental disorders, significantly contribute to MS patients’ risk of disability pension, a finding of relevance for MS management and treatment.

Childhood adversity and risk of suicide: cohort study of 548 721 adolescents and young adults in Sweden

Objective To examine the relation between childhood adversity, the role of school performance, and childhood psychopathology and the risk of suicide. Design Cohort study of register based indicators of childhood adversity (at ages 0-14) including death in the family (suicide analysed separately), parental substance abuse, parental psychiatric disorder, substantial parental criminality, parental separation/single parent household, receipt of public assistance, and residential instability. Setting Swedish medical birth register and various Swedish population based registers. Participants 548 721 individuals born 1987-91. Main outcome measures Estimates of suicide risk at ages 15-24 calculated as incidence rate ratios adjusted for time at risk and confounders. Results Adjusted incidence rate ratios for the relation between childhood adversity and suicide during adolescence and young adulthood ranged from 1.6 (95% confidence interval 1.1 to 2.4) for residential instability to 2.9 (1.4 to 5.9) for suicide in the family. There was a dose-response relation between accumulating childhood adversity and risk: 1.1 (0.9 to 1.4) for those exposed to one adversity and 1.9 (1.4 to 2.5) and 2.6 (1.9 to 3.4) for those exposed to two and three or more adversities, respectively. The association with increased risk of suicide remained even after adjustment for school performance and childhood psychopathology. Conclusion Childhood adversity is a risk factor for suicide in adolescence and young adulthood, particularly accumulated adversity. These results emphasise the importance of understanding the social mechanisms of suicide and the need for effective interventions early in life, aiming to alleviate the risk in disadvantaged children.

An Association between Initiation of Selective Serotonin Reuptake Inhibitors and Suicide - A Nationwide Register-Based Case-Crossover Study

Background Treatment with selective serotonin reuptake inhibitors (SSRI) is one of the most common treatments for depression. It is however not clear whether or not there is an increased short-term suicide risk during initiation with SSRI. Methods A register-based nationwide case-crossover study including 5,866 suicides, 1,698 women and 4,168 men, from the Death Register 2007-2010 in Sweden. SSRI initiation was defined as a dispensed prescription of SSRI within 28 days prior to the date of suicide with no previous dispensed prescription of SSRI within 4 months prior that prescription. The control period took place one year earlier. Odds ratio (OR) was estimated using conditional logistic regression. Result During the 28 day period prior to suicide 48 women and 138 men were exposed to SSRI initiation (while not being exposed in the control period) and 22 women and 43 men were exposed in the control period (while not being exposed in the case period). The OR for suicide after initiation with SSRI was 2.7 (95% CI: 1.6-44) for women, and 4.3 (95% CI: 3.0-6.1) for men. The highest OR was found 8-11 days after initiation with SSRI 9.7 (95% CI: 3.0-31.7) for women and men combined. Conclusion The main limitation in this study is confounding by indication, but the descriptive question is however not confounded by indication. Together with plausible biological mechanisms and previous clinical and epidemiological observations our findings, linking initiation of SSRI to increased short-term suicide risk, deserve further attention specifically in the clinical setting.