PURPOSE: Mortality among schizophrenia patients is substantially higher than in the general population. The aim of this study was to investigate, in a nationwide cohort of suicidal schizophrenic individuals, how the risks of suicide, severe suicide attempts and death are associated with usage of antidepressant or antipsychotic treatment.
METHODS: The study population included all individuals in Finland who were hospitalised with a diagnosis of attempted suicide between 1 January 1997 and 31 December 2003, who also had at least one hospitalisation due to schizophrenia diagnosis (ICD-10 F20), and were at least 16 years old when the index hospitalisation began. Cox's proportional hazards modelling and Bayesian intensity estimation were used in the analysis.
RESULTS: There were 1611 patients with a mean follow-up time of 4.3 years. Current use of antipsychotics was associated with decreased mortality due to suicide (HR 0.52, 95% CI 0.34-0.81, p = 0.004), but no significant decrease in mortality was observed during current use of antidepressants (0.66, 0.41-1.08, p = 0.099), when compared to past use. In more detailed analysis when current users were compared to non-users, olanzapine, and mixed use of antipsychotics, were associated with reduced all-cause mortality, and mixed use also with reduced risk of suicide mortality. Current use of citalopram was associated with decreased all-cause and suicide mortality.
CONCLUSIONS: In a population of suicidal schizophrenic individuals antipsychotic medication, treatment was associated with lower mortality from suicide and all-causes. Antidepressive medication was associated with lower all-cause mortality when used in combination with antipsychotics.
CONTEXT: People with severe mental illness (SMI) appear to have an elevated risk of death from cardiovascular disease, but results regarding cancer mortality are conflicting.
OBJECTIVE: To estimate this excess mortality and the contribution of antipsychotic medication, smoking, and social deprivation.
DESIGN: Retrospective cohort study.
SETTING: United Kingdom's General Practice Research Database. Patients Two cohorts were compared: people with SMI diagnoses and people without such diagnoses. Main Outcome Measure Mortality rates for coronary heart disease (CHD), stroke, and the 7 most common cancers in the United Kingdom.
RESULTS: A total of 46 136 people with SMI and 300 426 without SMI were selected for the study. Hazard ratios (HRs) for CHD mortality in people with SMI compared with controls were 3.22 (95% confidence interval [CI], 1.99-5.21) for people 18 through 49 years old, 1.86 (95% CI, 1.63-2.12) for those 50 through 75 years old, and 1.05 (95% CI, 0.92-1.19) for those older than 75 years. For stroke deaths, the HRs were 2.53 (95% CI, 0.99-6.47) for those younger than 50 years, 1.89 (95% CI, 1.50-2.38) for those 50 through 75 years old, and 1.34 (95% CI, 1.17-1.54) for those older than 75 years. The only significant result for cancer deaths was an unadjusted HR for respiratory tumors of 1.32 (95% CI, 1.04-1.68) for those 50 to 75 years old, which lost statistical significance after controlling for smoking and social deprivation. Increased HRs for CHD mortality occurred irrespective of sex, SMI diagnosis, or prescription of antipsychotic medication during follow-up. However, a higher prescribed dose of antipsychotics predicted greater risk of mortality from CHD and stroke.
CONCLUSIONS: This large community sample demonstrates that people with SMI have an increased risk of death from CHD and stroke that is not wholly explained by antipsychotic medication, smoking, or social deprivation scores. Rates of nonrespiratory cancer mortality were not raised. Further research is required concerning prevention of this mortality, including cardiovascular risk assessment, monitoring of antipsychotic medication, and attention to diet and exercise.
BACKGROUND: There is an excess of death from natural causes among people with schizophrenia.
AIMS: Schizophrenia and its treatment with neuroleptics were studied for their prediction of mortality in a representative population sample of 7217 Finns aged >/= 30 years.
METHOD: A comprehensive health examination was carried out at baseline. Schizophrenia was determined using the Present State Examination and previous medical records.
RESULTS: During a 17-year follow-up, 39 of the 99 people with schizophrenia died. Adjusted for age and gender, the relative mortality risk between those with schizophrenia and others was 2.84 (95% CI 2.06-3.90), and was 2.25 (95% CI1.61-3.15) after further adjusting for somatic diseases, bloodpressure, cholesterol, body mass index, smoking, exercise, alcohol intake and education. The number of neuroleptics used at the time of the baseline survey showed a graded relation to mortality. Adjusted for age, gender, somatic diseases and other potential risk factors for premature death, the relative risk was 2.50 (95% CI1.46-4.30) per increment of one neuroleptic.
CONCLUSIONS: There is an urgent need to ascertain whether the high mortality in schizophrenia is attributable to the disorder itself or the antipsychotic medication.
OBJETIVO: Estudiar la asociación entre los fármacos antipsicóticos prescritos y los resultados en la esquizofrenia o trastorno esquizoafectivo en la comunidad.
DISEÑO: Estudio prospectivo de cohorte utilizando registros centrales nacionales.
Emplazamiento Atención comunitaria en Finlandia.
PARTICIPANTES: A nivel nacional cohorte de 2.230 adultos consecutivos hospitalizados en Finlandia por primera vez a causa de la esquizofrenia o trastorno esquizoafectivo, desde enero 1995 hasta diciembre 2001.
Principales medidas de resultado: Las tasas de interrupción de los fármacos (todas las causas), las tasas de rehospitalización y la mortalidad asociadas a la monoterapia con los 10 fármacos antipsicóticos más utilizados. Se utilizaron modelos multivariados y métodos de puntuación de propensión para ajustar las estimaciones de efectividad.
RESULTADOS: El uso inicial de la clozapina (riesgo ajustado relativo 0,17, IC del 95% 0,10-0,29), depósito perfenazina (0,24, 0,13-0,47), y la olanzapina (0,35, 0,18 a 0,71) se asociaron con las tarifas más bajas de la interrupción de cualquier razón cuando se compara con haloperidol oral. Durante una media de seguimiento de 3,6 años, se registraron 4.640 casos de nueva hospitalización. El uso actual de depósito perfenazina (0,32, 0,22-0,49), olanzapina (0,54, 0,41 a 0,71), y la clozapina (0,64, 0,48 a 0,85) se asociaron con un menor riesgo de rehospitalización. El uso de haloperidol se asoció con un resultado pobre entre las mujeres. La mortalidad se elevó notablemente en pacientes que no toman antipsicóticos (12,3, 6,0 a 24,1) y el riesgo de suicidio fue alta (37,4, 5,1 a 276).
CONCLUSIONES: La efectividad de los antipsicóticos de primera y segunda generación varía en gran medida en la comunidad. Los pacientes tratados con perfenazina de depósito, clozapina, olanzapina o tienen un riesgo sustancialmente menor de rehospitalización o suspensión (por cualquier razón) de su tratamiento inicial que los pacientes tratados con haloperidol. El exceso de mortalidad se observa sobre todo en pacientes que no utilizan fármacos antipsicóticos.
OBJECTIVE: The goal of this 10-year naturalistic study was to examine, in clozapine-treated patients, the change in cardiovascular risk factors following clozapine initiation and the mortality estimates from cardiovascular disease.
METHOD: Data were collected from medical records from January 1992 to December 2003 and included age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation for clozapine-treated patients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Clozapine dosage and laboratory results were recorded at 12-month intervals.
RESULTS: At the time of clozapine initiation, the mean +/-?SD age of the 96 patients studied was 36.5 +/- 7.9 years; 28% (N = 27) were women. The Kaplan-Meier estimate for 10-year mortality from cardiovascular disease was 9%. African American and Hispanic American patients exhibited elevated risk of cardiovascular disease-related mortality (odds ratio [OR] = 7.2, p = .09; OR = 11.3, p = .04, respectively) compared to white patients. Body mass index (BMI) significantly increased the odds ratio of mortality (OR = 1.2, p < .01). The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43%, and Hispanic American (OR = 4.3, p = .027) and African American (OR = 11.5, p = .0001) patients showed elevated risks of developing diabetes mellitus compared to white patients. Additionally, BMI (OR = 1.11, p = .0006), total cholesterol level (OR = 1.006, p = .04), and serum triglyceride level (OR = 1.002, p = .04) modestly increased the odds ratio for the development of diabetes mellitus.
CONCLUSIONS: These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia.
This study compared the risks of cardiovascular morbidity and mortality in people with schizophrenia who use antipsychotic medications to risks in individuals without schizophrenia in a large managed care organization. A sample of 1920 schizophrenia patients was matched by age, sex, date, and health plan to 9600 persons randomly selected from the health plan general membership. Death, myocardial infarction, arrhythmia, and new-onset diabetes were identified using a National Death Index search and medical claims records. The adjusted all-cause mortality rate in the group of treated schizophrenics was four times higher than in the control group regardless of whether patients were given a typical or an atypical antipsychotic medication. Users of typical antipsychotics had a fivefold higher risk of myocardial infarction than the control subjects. Among patients with schizophrenia, cardiovascular risk was inversely associated with intensity of use of antipsychotic drugs, suggesting that the observed risks may not be due to a simple or direct effect of drugs. Patients treated for schizophrenia had higher rates of new-onset diabetes than did the general population controls. This risk was most pronounced in persons with more intense exposure to drugs and appeared to be indistinguishable in users of typical antipsychotics, of atypical products, or of both.
While premature death in schizophrenia is well recognised, mortality risk has received little longitudinal study in relation to population representativeness and patient engagement with health services. Within a rural Irish catchment area of socioeconomic, ethnic and geographical homogeneity and low residential mobility, an epidemiologically complete population of 72 patients with schizophrenia was followed up over 7.5 years in order to quantify mortality prospectively. Information was obtained in relation to 99% of the cohort, with 94% of those surviving retained in engagement with psychiatric care. There were 25 deaths (35% of cohort). A relative risk of 2.06 (95% CI, 1.40-2.80; P < 0.001) among this epidemiologically complete population may constitute an estimate of risk for mortality inherent to schizophrenia when disengagement from health services, residential mobility and socioeconomic, ethnic and geographical diversity are minimised. On long-term prospective evaluation, risk for death in schizophrenia was doubled on a background of enduring engagement in psychiatric care with increasing provision of community-based services and introduction of second-generation antipsychotics.
OBJECTIVE: To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls.
DESIGN: Cohort study of outpatients using administrative data.
SETTING: 3 US Medicaid programmes.
PARTICIPANTS: Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis.
MAIN OUTCOME MEASURE: Diagnosis of cardiac arrest or ventricular arrhythmia.
RESULTS: Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses > or =600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038).
CONCLUSIONS: The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect.
OBJECTIVE: The putative role of neuroleptics in the known excess mortality of subjects with schizophrenia remains disputed. The aim of this study was to assess the link between mortality and the class of neuroleptic.
METHOD: Causes of death (suicide, cardiovascular, etc.) and exposure to neuroleptics were studied in a cohort of 3474 patients with schizophrenia followed from 1993 to 1997.
RESULTS: From 1993 to 1997, 178 patients died. The risk of all-cause death (OR=1.59; 95% CI 1.02-2.50; p=0.04), and suicide (OR=2.22; 95% CI 1.24-3.97; p=0.006) were increased in users of thioxanthenes (alone or associated with other drugs), and increased risk of "other causes" of death was associated with use of atypical neuroleptics (OR=2.06; 95% CI 1.15-3.70; p=0.0016).
CONCLUSION: Our findings suggest the existence of association between certain classes of neuroleptics and death, all cause or specific. This could be related to the drug itself or to patient selection.
UNLABELLED: Overmortality in schizophrenic patients in comparison to the reference population has been found. At the present time this over mortality is mainly due to suicide or certain natural causes such as respiratory, cardio-vascular and cerebro-vascular diseases. In France there are not psychiatric cas registers that could allow us to study the mortality of psychiatric patients. The aim of the study was first to determine the standardized mortality ratio (SMR) in a group of 150 chronic schizophrenics followed during 8 years and secondly to detect the variables that could predict this mortality.
METHOD: The subjects filled out the RDC criteria for definite chronic schizophrenia and were included from 1991 to 1995. The subjects were inpatients or outpatients and their evaluation was made by psychiatrist. The subjects were selected from the different departments of two psychiatric hospitals corresponding to two French geographic areas (the Somme and Oise, two French "département"). At the initial assessment socio-demographic, clinical and psychometrical variables were collected: sex, age, educative level, number of hospitalizations, mean duration of the illness, scores on the Physical Anhedonia Scale, Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS). For the BPRS and PANSS, negative, positive and general subscales were extracted. In May 1999 all the subjects were contacted in order to know if they are alive or not and if they are death to know the date and the causes of their death. For the subjects that were still alive we used either direct assessment by interview of their psychiatrist or general practioner or indirect assessment by interview of their family. For the deceased subjects, we obtained informations about the date and the causes of the death by their psychiatrist or general practioner. If the patients were lost sight of we send a letter to the city of their place of birth in order to know if they are alive or not and if they are dead to know the date of their death. Moreover demographic data concerning the French and the Somme populations as well as the corresponding data concerning the mortality according to age and gender were obtained. A comparison of global mortality between patients and the French general or the Somme populations was made by the SMR. Moreover the deceased subjects and the survivors were compared by unidimensional statistical tests (chi 2 analyses for qualitative variables or Student's t test for quantitative variables) for the sociodemographic, clinical or psychometric variables. For each significant difference at p level < or = 0.05, the corresponding variable was retained for a multivariate step by step discriminant analysis.
RESULTS: We found 13 deaths (10 males, 3 females): 3 suicides, 3 cardiac diseases, 2 cancers, 1 respiratory disease, 1 car crash, 1 homicide, 1 infectious disease, 1 respiratory arrest. The mortality rate (without correction for age) were 1.08% for both sexes, 1.44% and 0.6% for males and females respectively. The mortality rates (corrected for age) were 2.47% in our cohort and 0.988% in the Somme population. The corresponding SMR was 2.5. (chi 2 = 3.15, df = 1, p < 0.01). The overmortality was found only for males (chi 2 = 2.57, df = 1, p < 0.01) and not for females (chi 2 = 0.034, df = 1, p > 0.05). Concerning the comparisons between the deceased subjects and the survivors, there were five significant differences: gender, age, duration of the illness, neuroleptic dosage, negative symptoms (BPRS negative subscale). The deceased subjects were older, there was more men, the duration of the illness and the neuroleptic dosage were higher and the BPRS negative subscale was lower. These five variables were introduced in the discriminant analysis to explore notably their respecting weight. The corresponding power of the five variables were in decreasing order: neuroleptic dosage, negative symptoms, age, gender, duration of the illness.
DISCUSSION: Our study confirm the overmortality in schizophrenic patients, this overmortality was especially explained by natural and non natural causes of death. The overmortality concerned only schizophrenic males patients whereas schizophrenic females did not have an overmortality. This negative result could be explain by a bias selection, the males being overrepresented in our cohort. Among the variables that were linked to the overmortality, the low level of negative symptomatology confirmed previous studies that have shown a low suicide rate in deficit schizophrenic. Moreover a high level of positive symptomatology could lead to high risk behaviors (suicide attempts, sexual disinhibition...). The neuroleptic dosage was the variable whom discriminate power was the highest. At least two explanations can be proposed. (ABSTRACT TRUNCATED)
Mortality among schizophrenia patients is substantially higher than in the general population. The aim of this study was to investigate, in a nationwide cohort of suicidal schizophrenic individuals, how the risks of suicide, severe suicide attempts and death are associated with usage of antidepressant or antipsychotic treatment.
METHODS:
The study population included all individuals in Finland who were hospitalised with a diagnosis of attempted suicide between 1 January 1997 and 31 December 2003, who also had at least one hospitalisation due to schizophrenia diagnosis (ICD-10 F20), and were at least 16 years old when the index hospitalisation began. Cox's proportional hazards modelling and Bayesian intensity estimation were used in the analysis.
RESULTS:
There were 1611 patients with a mean follow-up time of 4.3 years. Current use of antipsychotics was associated with decreased mortality due to suicide (HR 0.52, 95% CI 0.34-0.81, p = 0.004), but no significant decrease in mortality was observed during current use of antidepressants (0.66, 0.41-1.08, p = 0.099), when compared to past use. In more detailed analysis when current users were compared to non-users, olanzapine, and mixed use of antipsychotics, were associated with reduced all-cause mortality, and mixed use also with reduced risk of suicide mortality. Current use of citalopram was associated with decreased all-cause and suicide mortality.
CONCLUSIONS:
In a population of suicidal schizophrenic individuals antipsychotic medication, treatment was associated with lower mortality from suicide and all-causes. Antidepressive medication was associated with lower all-cause mortality when used in combination with antipsychotics.
