Antipsychotic medications and severe sepsis in schizophrenia: A nested case-control study.

BACKGROUND: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. METHODS: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations. RESULTS: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. CONCLUSION: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients.

Prevalence and 3-year incidence of physical illnesses after schizophrenia diagnosis: Comparison with general population.

AIM: People with schizophrenia are at a greater risk of poor physical health than the general population. This study investigated the annual incidence of physical illnesses after a new schizophrenia diagnosis, which has rarely been investigated in the literature. METHODS: The authors collected data from Taiwan's National Health Insurance Research Database from January 1, 1996, to December 31, 2013, and enrolled 1910 patients with newly diagnosed schizophrenia cases aged 10-40 years and 7640 age- and sex-matched controls from the general population. They estimated the 1-year prevalence and annual incidence rate ratio (IRR) of specified physical diseases across 3 years in the schizophrenia group compared with the controls. RESULTS: Several physical illnesses were prevalent within 1 year of schizophrenia diagnosis. Regarding incident physical illnesses, patients had a moderate to strong risk of numerous physical illnesses (IRR > 3.0: ischemic heart disease, cerebrovascular disease, diabetes mellitus, and cancer; IRR 1.8-3.0: other forms of heart disease, vein and lymphatic diseases, pneumonia, chronic hepatic disease, and ulcer disease) within the first year after schizophrenia diagnosis. The IRRs of most physical illnesses declined over 3 years, except for that of cerebrovascular disease, which significantly increased (IRR > 3.0) over the 3 years after schizophrenia diagnosis. Cerebrovascular disease had a significant incidence risk (IRR > 3) persistently across the 3 years. CONCLUSION: Various comorbid physical illnesses can occur in the early stages of schizophrenia. Clinicians should consider these vulnerabilities to physical illnesses during the evaluation of patients with newly diagnosed schizophrenia by attempting to prevent, screen for, and manage them.

Incidence and Risk Profiles for Suicide Mortality in Patients With Schizophrenia Receiving Homecare Case Management in Taiwan.

Case management (CM)-based community therapy for patients with schizophrenia had little effect on reducing suicide mortality. We investigate the long-term suicide mortality outcome and associated risk factors in patients with schizophrenia receiving homecare (CM) in Taiwan. We enrolled a nationwide cohort of patients with schizophrenia who newly received homecare CM intervention (n = 13 317) between January 1, 2001, and December 31, 2015; their data were derived from Taiwan's National Health Insurance Research Database. We calculated the incidence rate of suicide methods. We examined the demographic and medical utilization profile for suicide and then performed a nested case-control study and multivariate regression to identify independent risk factors for suicide mortality. Among the 13 317 patients who received homecare CM intervention, 1766 died during the study period, of whom 213 died by suicide, which is the leading cause of unnatural death. Jumping from a high place, self-poisoning, and hanging were the top 3 suicide methods. Increased medical utilization was noted for both psychiatric and non-psychiatric services within 3 months of suicide mortality. Comorbidities of depressive disorder, nonspecific heart diseases, pneumonia, and gastrointestinal ulcers were identified as independent risk factors for suicide mortality. Suicide was the leading cause of unnatural mortality in patients with schizophrenia receiving homecare CM intervention in Taiwan. We noted the preferred suicide methods, high medical utilization, and comorbidities before suicide. Thus, we suggest that the CM team should assess lethal methods for suicide and ensure that patients adhere to psychiatry treatment for improving the current care model for this specified population.

Incidence of and risk factors for alcohol dependence in bipolar disorder: A population-based cohort and nested case-control study.

OBJECTIVES: Although alcohol dependence is highly prevalent in patients with bipolar disorder, the causal relationship is not yet well-established. This study estimated the incidence of alcohol dependence in a nationwide bipolar disorder cohort and examined risk factors for alcohol dependence. METHODS: Patients aged 15-65 years with consistent bipolar disorder who had their first psychiatric admission between 1999 and 2012 (n = 21,791) were enrolled from the National Health Insurance Research Database in Taiwan. We calculated the adjusted incidence rate ratio of alcohol dependence in the bipolar cohort relative to the general population after stratification by age and sex. In the nested case-control study, we included patients with incident alcohol dependence as cases and four age- and sex-matched controls for each case to analyze health care utilization, comorbidities and concomitant medications between them. RESULTS: We identified 1261 patients with bipolar disorder with incident alcohol dependence. Relative to the general population, the adjusted incidence rate ratio of alcohol dependence was 9.20 in the bipolar cohort. All adjusted incidence rate ratios were high across all age subgroups. Cases had higher psychiatric and nonpsychiatric health care utilization than did controls. Multivariate analysis revealed that cases tended to have cardiovascular disease, diabetes mellitus, chronic hepatic disease, pneumonia and delirium before alcohol dependence diagnosis. Cases had higher psychiatric comorbidities, namely drug-induced mental disorders, anxiety disorder, personality disorder, adjustment disorder and sleep disorder. CONCLUSION: The bipolar cohort had a higher incidence of alcohol dependence. We identified specific groups with a high risk of alcohol dependence. Additional strategies for early detection, treatment and intervention for alcohol dependence should be developed.

Excess mortality and risk factors for mortality among patients with severe mental disorders receiving home care case management.

AIM: Home care case management (CM) is the main intervention for patients with severe mental disorders (SMDs) requiring outreach care. This study investigated the long-term mortality outcome and associated risk factors in patients who received home care CM. METHODS: This nationwide study enrolled patients who received home care CM (n = 10,255) between 1 January 1999 and 31 December 2010. Each patient was followed up from the baseline (when patients underwent home case CM for the first time during the study period) to the censor (i.e. mortality or the end of the study). We calculated the standardized mortality ratio (SMR) and presented by age and diagnosis. Multivariate regression was performed to assess independent risk factors for mortality. RESULTS: Among 10,255 patients who received home care CM, 1409 died during the study period; the overall SMR was 3.13. Specifically, patients with organic mental disorder had the highest SMR (4.98), followed by those with schizophrenia (3.89), major depression (2.98), and bipolar disorder (1.97). In the multivariate analysis, patients with organic mental disorder or dementia had the highest risk, whereas the mortality risk in patients with schizophrenia was comparable to that in patients with bipolar disorder or major depression. Deceased patients had a significantly higher proportion of acute or chronic physical illnesses, including cancer, chronic hepatic disease, pneumonia, diabetes mellitus, cardiovascular disease, and asthma. CONCLUSION: This study presented the gap of mortality in patients with SMDs receiving home care CM in Taiwan. We highlight the need for effective strategies to improve medical care for this specified population.

Age effect of antipsychotic medications on the risk of sudden cardiac death in patients with schizophrenia: A nationwide case-crossover study.

AIM: Research regarding the effects of age in patients with schizophrenia taking antipsychotics on the risk of sudden cardiac death is lacking. We determined the effect of patient age on the association between exposure to antipsychotics and the risk of sudden cardiac death in a nationwide schizophrenia cohort. METHODS: From the Taiwan National Health Insurance Research Database and Department of Health Death Certification System, data of 1836 patients with schizophrenia who had experienced sudden cardiac death between 2000 and 2016 were included. A case-crossover design by using a 14-day window was applied, and subgroup analyses were performed by stratifying patients into three age subgroups (<45, 45-65, and >65 years) to assess the effect of age on the risk of sudden cardiac death in patients taking antipsychotics. RESULTS: No association between exposure to antipsychotic agents and sudden cardiac death risk was found in patients aged >65 years who were characterized by a high burden of medical illnesses. However, zotepine significantly increased the risk of sudden cardiac death in patients aged <45 years (adjusted relative risk [RR] = 2.68, P = 0.046). Flupentixol (adjusted RR = 5.30, P = 0.004) and risperidone (adjusted RR = 1.68, P = 0.01) significantly elevated the risk of sudden cardiac death in patients aged 45-65 years. CONCLUSION: This study suggests that individual antipsychotics pose different risks of sudden cardiac death in patients with schizophrenia across their lifespan. Clinicians should consider patient age when evaluating the risks and benefits of antipsychotic treatment.

Antipsychotic medications and the progression of upper respiratory infection to pneumonia in patients with schizophrenia.

Aim Research regarding the effect of antipsychotic medications on the risk of upper respiratory infection (URI) progression to pneumonia in patients with schizophrenia is rare. This study investigated the effect of antipsychotic use on the risk of URI progression to pneumonia in patients with schizophrenia. METHODS: This cohort study used the Taiwan's Nationwide Psychiatric Inpatient Medical Claims Database. From January 1, 1996 to December 31, 2012, 22,771 patients with schizophrenia were diagnosed as having the first URI episode after their first psychiatric admission and 135 of them developed pneumonia within 30 days. The duration and dosage of antipsychotics were assessed before and after URI. Cox regression with time-dependent model was used to assess the risk of antipsychotic use on the progression of URI to pneumonia. RESULTS: Among first- and second-generation antipsychotics, clozapine was the only medication associated with an increased risk of developing pneumonia before URI (adjusted hazard ratio [aHR] = 2.05, P = .024). Clozapine was also the only drug significantly associated with an increased risk after URI (aHR = 1.92, P = .027). Regarding medication use after URI, the dosage of clozapine was significantly associated with an increased risk based on Cox regression with a time-dependent model (aHR = 1.95, P = .003). CONCLUSIONS: The use of clozapine was associated with URI progression to pneumonia in patients with schizophrenia. The dosage of clozapine used in the post-URI period was also associated with an increased risk. Clinicians should consider lowering clozapine dosage in patients with URI to prevent them developing pneumonia.

Physical Illnesses Before Diagnosed as Schizophrenia: A Nationwide Case-Control Study.

Some physical illnesses are potentially associated with the development of schizophrenia. However, few studies have investigated these associations. Here, we examined physical illnesses and medical utilization patterns existing before patients received a diagnosis of schizophrenia. We enrolled a large representative cohort of the general population in Taiwan (N = 1 000 000) and identified 1969 young patients with a new diagnosis of schizophrenia from January 1, 2000 to December 31, 2013. We conducted a nested case-control study based on risk-set sampling. Each case was age-matched and sex-matched with 4 controls selected from the general population. The case and control groups were compared on the basis of various clinical characteristics. Conditional logistic regression was used to estimate the magnitude of risk associated with newly diagnosed schizophrenia. Within the 1 year before the schizophrenia diagnosis, the cases were most likely to visit the psychiatry department, followed by internal medicine and family medicine departments. According to multivariate analysis, compared with the controls, the cases had substantially higher risk of physical conditions in the prodromal phase, including hypertension (adjusted risk ratio [aRR] = 1.93, P = .001), other forms of heart disease (aRR = 2.07, P < .001), cerebrovascular diseases (aRR = 2.96, P = .001), chronic obstructive pulmonary disease (aRR = 1.50, P = .005), asthma (aRR = 1.76, P = .003), and irritable bowel syndrome (aRR = 2.00, P < .001). A wide range of psychiatric diseases and concomitant use of medications were significantly associated with schizophrenia development. In conclusion, several physical illnesses were identified to be associated with schizophrenia development, indicating that people with these illnesses could be vulnerable to schizophrenia.

Identification and medical utilization of newly diagnosed panic disorder: A Nationwide case-control study.

OBJECTIVE: Ascertaining comorbid illnesses and patterns of medical utilization early in the course of psychiatric illness can help identify patients with panic disorder. We investigated how such cases were diagnosed and the comorbidities associated with newly diagnosed panic disorder in a nationwide database. METHODS: We enrolled a large representative cohort of the general population in Taiwan (N = 1000,000) and selected 9759 cases of panic disorder from January 1, 2000 to December 31, 2013. The distribution of the departments in which the cases were identified and the medical utilization 12 months before diagnosis were analyzed. Based on a nested case-control study, four controls were randomly selected for each case and matched for sex, age, and incidence year. Conditional logistic regression was used to explore the factors associated with newly-diagnosed panic disorder such as demographic factors, concomitant medications, and physical and psychiatric comorbidities. RESULTS: Most (58.5%) cases of panic disorder were diagnosed in the psychiatry department, whereas only 3.7% were identified in the emergency department. Before diagnosis, the patients frequently visited the departments of internal medicine, family practice, and Chinese herbal medicine. A multivariate analysis revealed a higher number of physical and psychiatric comorbidities before diagnosis in the cases compared with the controls, especially depressive disorder and other anxiety disorders. CONCLUSIONS: Individuals with certain comorbidities and patterns of medical utilization are more likely to be diagnosed with panic disorder. We suggest providing more training to general practitioners and emergency physicians for the early diagnosis of panic disorder.

Nationwide analysis of medical utilization in people with severe mental illness receiving home care case management.

AIM: This nationwide study investigated the change in medical utilization of psychiatric home care case management (CM). METHODS: This nationwide study enrolled patients receiving CM (N = 10,274) from January 1, 1999 to December 31, 2010, from Taiwan's National Health Insurance Research Database. Through a 2-year mirror-image comparison weighted by the contributed person-time for each subject, we evaluated changes in medical utilization. Furthermore, a case-crossover analysis was used to verify the independent effect of CM in changing medical utilization by adjusting the time-variant variables between the pre-2-year (within 2 years before receiving CM) and post-2-year (within years after receiving CM) periods. The same methodology was applied for the subsequent 2-year comparison to assess the maintenance effect. RESULTS: Of the 10,274 patients receiving CM, 69.7% had schizophrenia. The results showed a chronological trend for the intervention of CM. The adjusted mirror-image analysis revealed a significant decrement of psychiatric and involuntary admissions after the intervention, and the utilization shifted toward psychiatric outpatient service. The case-crossover analysis with the adjustment of time-variant covariates confirmed the independent effect of CM on the changes of medical utilization. The comparable effect persisted after the next 2 years of intervention. However, CM showed no impact on lowering the admission rate for comorbid physical illnesses after the intervention. CONCLUSIONS: The CM model can effectively reduce psychiatric hospitalization and involuntary admission frequency but has no effect on comorbid physical illnesses. Care models aimed at ameliorating physical problems in such patients are needed.

Mood stabilisers and risk of stroke in bipolar disorder.

BACKGROUND: Research on the risk of stroke following the use of mood stabilisers specific to patients with bipolar disorder is limited.AimsIn this study, we investigated the risk of stroke following the exposure to mood stabilisers in patients with bipolar disorder. METHOD: Data for this nationwide population-based study were derived from the Taiwan National Health Insurance Research Database. Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609 new-onset cases of stroke were identified from 1999 to 2012. A case-crossover study design utilising 14-day windows was applied to assess the acute exposure effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and other types of stroke in patients with bipolar disorder. RESULTS: Mood stabilisers as a group were significantly associated with the increased risk of stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041). Among individual mood stabilisers, acute exposure to carbamazepine had the highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke. CONCLUSIONS: Use of carbamazepine and valproic acid, but not lithium and lamotrigine, is associated with increased risk of stroke in patients with bipolar disorder.Declaration of interestNone.

Identification and medical utilization of incident cases of alcohol dependence: A population-based case-control study.

BACKGROUND: Patients with alcohol dependence (AD) often seek help from medical professionals due to alcohol-related diseases, but the overall distribution of medical specialties identifying new AD cases is unclear. We investigated how such cases were identified and how medical resources were utilized before the identification of AD in a nationwide cohort. METHODS: We enrolled a population-based cohort (N = 1,000,000) using the National Health Insurance Research Database of Taiwan; 8181 cases with incident AD were retrieved between January 1, 2000, and December 31, 2010. For this nested case-control study, four controls were matched for age and sex with each case based on risk-set sampling. We measured various dimensions of medical utilization before AD was diagnosed, including department visited, physical comorbidity, and medication used. Conditional logistic regression was used for estimating the variables associated with AD. RESULTS: Patients living in less urbanized areas who were unemployed were more likely to develop AD. The highest proportions (34.2%) of AD cases were identified in the internal medicine department, followed by the emergency (22.3%) and psychiatry (18.7%) departments. AD patients had a higher risk of comorbid chronic hepatic disease (adjusted RR = 2.72, p < 0.001) before identification of AD than controls. AD patients also had greater numbers of hospital admissions than controls, including non-psychiatric and psychiatric hospitalizations. Outpatient visit numbers were similar for AD patients and controls. CONCLUSIONS: The findings indicate that clinicians providing care in diverse medical settings should be prepared to screen for unhealthy alcohol use and to mitigate its detrimental effects.