Christiane Gasse

Somatic Hospital Contacts, Invasive Cardiac Procedures, and Mortality From Heart Disease in Patients With Severe Mental Disorder

CONTEXT Excess mortality from heart disease is observed in patients with severe mental disorder. This excess mortality may be rooted in adverse effects of pharmacological or psychotropic treatment, lifestyle factors, or inadequate somatic care. OBJECTIVES To examine whether persons with severe mental disorder, defined as persons admitted to a psychiatric hospital with bipolar affective disorder, schizoaffective disorder, or schizophrenia, are in contact with hospitals and undergoing invasive procedures for heart disease to the same degree as the nonpsychiatric general population, and to determine whether they have higher mortality rates of heart disease. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort of 4.6 million persons born in Denmark was followed up from 1994 to 2007. Rates of mortality, somatic contacts, and invasive procedures were estimated by survival analysis. MAIN OUTCOME MEASURES Incidence rate ratios of heart disease admissions and heart disease mortality as well as probability of invasive cardiac procedures. RESULTS The incidence rate ratio of heart disease contacts in persons with severe mental disorder compared with the rate for the nonpsychiatric general population was only slightly increased, at 1.11 (95% confidence interval, 1.08-1.14). In contrast, their excess mortality rate ratio from heart disease was 2.90 (95% confidence interval, 2.71-3.10). Five years after the first contact for somatic heart disease, the risk of dying of heart disease was 8.26% for persons with severe mental disorder (aged <70 years) but only 2.86% in patients with heart disease who had never been admitted to a psychiatric hospital. The fraction undergoing invasive procedures within 5 years was reduced among patients with severe mental disorder as compared with the nonpsychiatric general population (7.04% vs 12.27%, respectively). CONCLUSIONS Individuals with severe mental disorder had only negligible excess rates of contact for heart disease. Given their excess mortality from heart disease and lower rates of invasive procedures after first contact, it would seem that the treatment for heart disease offered to these individuals in Denmark is neither sufficiently efficient nor sufficiently intensive. This undertreatment may explain part of their excess mortality.

Chronic Somatic Comorbidity and Excess Mortality Due to Natural Causes in Persons with Schizophrenia or Bipolar Affective Disorder

Background Suicide and death by accidents in persons with schizophrenia and bipolar disorder are common, but excess mortality from natural death accounts for even more years of life lost. The impact of somatic comorbidity, however, often is not duly considered in analyses and explanations of excess mortality in patients with psychotic disorders. Objective/Methods This study investigates and evaluates the impact of 19 severe chronic diseases on excess mortality due to diseases and medical conditions (natural death) in individuals with psychotic disorders compared with the general population using a population-based cohort study in Denmark. Incidence/mortality rate ratios of admission/mortality were calculated using survival analysis. Results Cohort members with psychotic disorders had higher incidence rates of hospital contacts for almost all of the 19 disorders than the general population. The mortality rate ratio (MRR) of natural death was 7.10 (95% CI 6.45, 7.81) for schizophrenic men, decreasing to 4.64 (95% CI 4.21, 5.10) after adjustment for the somatic disorders. The same pattern existed in women and in both genders with bipolar disorder. Highest MRRs were observed for psychotic patients without hospital admissions with the investigated somatic disorders. Conclusion Chronic somatic diseases accounted for half of the excess mortality in patients with schizophrenia or bipolar disorder. Chronic disorders investigated in this paper seem to be under-treated or under-detected among such patients.

Antipsychotic Polypharmacy and Risk of Death From Natural Causes in Patients With Schizophrenia: A Population-Based Nested Case-Control Study

OBJECTIVE Concomitant prescription of more than 1 antipsychotic agent (antipsychotic polypharmacy) in the treatment of schizophrenia is prevalent, although monotherapy is generally recommended. Mortality from natural causes is markedly increased in schizophrenia, and the role of polypharmacy remains controversial. The objective was to investigate if antipsychotic polypharmacy is associated with the excess mortality from natural causes among patients with schizophrenia. METHOD A population-based nested case-control study was conducted using patient data from January 1, 1996, to December 31, 2005, obtained from central Danish registers. From the study population of 27,633 patients with ICD-8- and ICD-10-diagnosed schizophrenia or other mainly nonaffective psychoses, aged 18-53 years, we identified 193 cases who died of natural causes within a 2-year period and 1,937 age- and sex-matched controls. Current drug use was defined as at least 1 prescription filled within 90 days before the date of death or the index date. The data were analyzed by conditional logistic regression. RESULTS Risk of natural death did not increase with the number of concurrently used antipsychotic agents compared with antipsychotic monotherapy (no antipsychotics: adjusted odds ratio [OR] = 1.48 [95% CI, 0.89-2.46]; 2 antipsychotics: OR = 0.91 [95% CI, 0.61-1.36]; 3 or more antipsychotics: OR = 1.16 [95% CI, 0.68-2.00]). Current use of benzodiazepine derivatives with long elimination half-lives (more than 24 hours) was associated with increased risk of natural death in patients with schizophrenia treated with antipsychotics (OR = 1.78 [95% CI, 1.25-2.52]). CONCLUSIONS Antipsychotic polypharmacy did not contribute to the excess mortality from natural causes in middle-aged patients with schizophrenia. The detected increased risk of death associated with benzodiazepines with long elimination half-lives calls for further clarification.

Frequent use of opioids in patients with dementia and nursing home residents: A study of the entire elderly population of Denmark

Pain is believed to be undertreated in patients with dementia; however, no larger studies have been conducted. The aim was to investigate prevalent use of opioids in elderly with and without dementia in the entire elderly population of Denmark.

Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study

BACKGROUND Identification of patients at high risk of treatment-resistant schizophrenia at the time of schizophrenia diagnosis would be of great clinical benefit in minimising the delay to clozapine treatment in patients unlikely to respond to non-clozapine antipsychotics. However, little is known about predictors of treatment resistance in this patient population. We used a treatment-based proxy for treatment-resistant schizophrenia to identify candidate predictors of treatment resistance at first hospital contact with a schizophrenia diagnosis. METHODS In this population-based cohort study, we obtained Danish national registry data for all adult patients (≥18 years) with incident schizophrenia diagnosed between Jan 1, 1996, and Dec 31, 2006, and followed up until Dec 31, 2010. Our main proxy definition of treatment-resistant schizophrenia was the earliest instance of either clozapine initiation or hospital admission for schizophrenia after having had two periods of different antipsychotic monotherapy. We did multivariable Cox proportional hazards regression analysis to estimate the association between baseline candidate predictors and treatment resistance. FINDINGS 8624 patients fulfilled the criteria for inclusion. In multivariable complete-case analyses, 1703 (21%) of 8044 patients fulfilled the main proxy definition of treatment-resistant schizophrenia during a median follow-up of 9·1 years (IQR 6·3-11·9). Younger age (hazard ratio 0·96 [95% CI 0·95-0·97]), living in a less urban area (provincial 1·38 [1·23-1·56], rural 1·44 [1·25-1·65]), primary education level (0·88 [0·79-0·98]), more than 30 bed-days in psychiatric hospital in the year before first schizophrenia diagnosis (1·54 [1·35-1·75]), inpatient at first schizophrenia diagnosis (2·07 [1·87-2·29]), paranoid subtype (1·24 [1·13-1·37]), comorbid personality disorder (1·24 [1·11-1·39]), psychotropic drug use (antipsychotics 1·51 [1·35-1·69], antidepressants 1·15 [1·03-1·29], and benzodiazepines 1·22 [1·10-1·37]), and previous suicide attempt (1·21 [1·07-1·39]) were all significantly associated with treatment-resistant schizophrenia. INTERPRETATION Our study identifies several candidate predictors that could potentially be included in future prediction models for treatment-resistant schizophrenia. Notably, established risk factors for schizophrenia did not predict treatment resistance, suggesting that treatment-resistant disease might be a distinct subtype of schizophrenia and not merely a more severe form. FUNDING European Communitys Seventh Framework Programme.

Prevalence of antidepressant use and contacts with psychiatrists and psychologists in pregnant and postpartum women

Munk‐Olsen T, Gasse C, Laursen TM. Prevalence of antidepressant use and contacts with psychiatrists and psychologists in pregnant and postpartum women.

Cardiovascular drug use and mortality in patients with schizophrenia or bipolar disorder: a Danish population-based study

BACKGROUND Cardiovascular (CV) co-morbidity is one of the major modifiable risk factors driving the excess mortality in individuals with schizophrenia or bipolar disorder. Population-based studies in this area are sparse. METHOD We used Danish population registers to calculate incidence rate ratios (IRRs) for CV drug use, and mortality rate ratios comparing subjects with schizophrenia or bipolar disorder with subjects with no prior psychiatric hospitalization. RESULTS IRRs for CV prescriptions were significantly decreased in patients with schizophrenia or bipolar disorder compared with the general population. Among persons without previous myocardial infarction (MI) or cerebrovascular disease, persons with schizophrenia or bipolar disorder had an up to 6- and 15-fold increased mortality from all causes or unnatural causes, respectively, compared with the general population, being most pronounced among those without CV treatment (16-fold increase). Among those with previous MI or cerebrovascular disease, excess all-cause and unnatural death was lower (up to 3-fold and 7-fold increased, respectively), but was similar in CV-treated and -untreated persons. CONCLUSIONS The present study shows an apparent under-prescription of most CV drugs among patients with schizophrenia or bipolar disorder compared with the general population in Denmark. The excess of mortality by unnatural deaths in the untreated group suggests that the association between CV treatment and mortality may be confounded by severity of illness. However, our results also suggest that treatment of CV risk factors is neglected in these patients.

Inflammation and depression: combined use of selective serotonin reuptake inhibitors and NSAIDs or paracetamol and psychiatric outcomes

Nonsteroidal anti‐inflammatory drugs (NSAIDs) and paracetamol have been shown to yield the potential of adjunctive antidepressant treatment effects to selective serotonin reuptake inhibitors (SSRIs); however, when investigating treatment effects of concomitant use, simultaneous evaluation of potential adverse events is important. The objective was thus to investigate treatment effectiveness and safety aspects of concomitant SSRI use with NSAIDs or paracetamol.

The Effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study

OBJECTIVE Both preclinical studies and clinical trials have indicated that the combination of a selective serotonin reuptake inhibitor (SSRI) and a statin may have superior antidepressant effects compared with SSRI treatment alone. The authors sought to assess whether this beneficial effect can be generalized to a more heterogeneous population of SSRI users. METHOD In a nationwide cohort study that included all incident SSRI users in Denmark between 1997 and 2012, the authors compared people who had periods of concomitant use of SSRIs and statins with people who had periods of SSRI treatment alone. Outcomes included the rates of psychiatric hospital contacts (any cause), psychiatric hospital contacts due to depression, suicidal behavior, and all-cause mortality. Using Cox regression and competing risk analysis, the authors calculated crude and adjusted hazard ratios for these outcomes. RESULTS The authors identified 872,216 incident SSRI users, of whom 113,108 (13.0%) used a statin concomitantly. Compared with SSRI treatment alone, the combined use of an SSRI and a statin was associated with a significantly lower risk for both psychiatric hospital contacts (adjusted hazard ratio=0.75 (95% CI=0.69, 0.82) and psychiatric hospital contacts due to depression (adjusted hazard ratio=0.64, 95% CI=0.55, 0.75). Compared with SSRI treatment alone, the concomitant use of SSRIs and statins was not associated with significant increases in all-cause mortality (adjusted hazard ratio=1.04, 95% CI=0.96, 1.12) or suicidal behavior (adjusted hazard ratio=0.85, 95% CI=0.61, 1.18). CONCLUSIONS In a large naturalistic cohort, concomitant treatment with SSRIs and statins resulted in robust advantages compared with SSRIs alone.

Time Trends in Antipsychotic Drug Use in Patients with Dementia: A Nationwide Study

BACKGROUND Antipsychotics are often used to treat neuropsychiatric symptoms in dementia, but the evidence for effect is limited. Antipsychotics have been associated with increased risk of adverse events and mortality in patients with dementia, leading to safety regulations worldwide. OBJECTIVE To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012. The decreasing use of antipsychotics was accompanied by decreasing use of anxiolytics and hypnotics/sedatives, but an increase in the use of antidepressants from 43.3% in 2000 to 53.8% in 2012. These changes were significant across almost all age groups. Treatment intensity among patients using antipsychotics increased as the annual median number of defined daily doses (DDD) increased from 33.3 to 42.0 DDD. CONCLUSIONS The changing patterns of psychotropic drug use may be caused by warnings against use of antipsychotics. Further research is needed to explore the implications for patient safety.