Shang Ying Tsai

Second-Generation Antipsychotic Medications and Risk of Pneumonia in Schizophrenia

This study assessed the association between second-generation antipsychotic medications and risk of pneumonia requiring hospitalization in patients with schizophrenia because the evidence is limited in the population. We enrolled a nationwide cohort of 33,024 inpatients with schizophrenia ranged in age from 18 to 65 years, who were derived from the National Health Insurance Research Database in Taiwan from 2000 to 2008. Cases (n = 1741) were defined as patients who developed pneumonia after their first psychiatric admissions. Risk set sampling was used to match each case with 4 controls by age, sex, and the year of the first admission based on nested case-control study. Antipsychotic exposure was categorized by type, duration, and daily dose, and the association between exposure and pneumonia was assessed using conditional logistic regression. We found that current use of clozapine (adjusted risk ratio = 3.18, 95% CI: 2.62-3.86, P < .001) was associated with a dose-dependent increase in the risk. Although quetiapine, olanzapine, zotepine, and risperidone were associated with increased risk, there was no clear dose-dependent relationship. Amisulpride was associated with a low risk of pneumonia. The use of clozapine combined with another drug (olanzapine, quetiapine, zotepine, risperidone, or amisulpride), as assessed separately, was associated with increased risk for pneumonia. In addition, with the exception of amisulpride, each drug was associated with increased risk for pneumonia at the beginning of treatment. Clinicians who prescribe clozapine to patients with schizophrenia should closely monitor them for pneumonia, particularly at the start of therapy and when clozapine is combined with other antipsychotics.

Suicide by charcoal burning in Taiwan: implications for means substitution by a case-linkage study

ObjectiveThis study estimated the incidence of suicide mortality among suicide attempters in Taiwan and assessed the extent of means substitution among subjects with a non-fatal attempt and a subsequent fatal attempt during the study period.MethodsA total of 5,261 suicide attempters registered in a surveillance system of a metropolitan catchment area from 2004 to 2005 were followed through 2005. Linkage to the death certification system revealed that 72 died by suicide. The association of completed suicide with the suicide method used at index attempt was examined using Cox proportional hazards regression. Incidence rate for the subsequent lethal suicide was estimated based on life tables.ResultsThe 1-year incidence rate of suicide mortality was 0.017: 0.026 in males and 0.013 in females. There was a strong association between burning charcoal as the method used at the index attempt (relative hazardxa0=xa04.1, Pxa0<xa00.001) and completed suicides. Those who used the method of burning charcoal at the index attempt frequently used the same means in a subsequent attempt leading to suicide mortality. However, a majority of suicide completers (59.1%) who died by burning charcoal had used a different method at their index attempt.ConclusionsPersons who attempt suicide by charcoal burning are a high-risk group for completed suicide. Those who burned charcoal in a suicide attempt were likely to use the same method in a later lethal attempt, and charcoal burning was a frequent cause of death among those who used different methods in earlier attempts. Charcoal burning should be a target for suicide prevention efforts.

Causes of Death of Patients with Methamphetamine Dependence: A Record-Linkage Study

INTRODUCTION AND AIMSnMethamphetamine use leads to increased likelihood of premature death. The authors investigated the causes of death and risk of mortality in a large cohort of patients with methamphetamine dependence.nnnDESIGN AND METHODSnA cohort of 1254 subjects with methamphetamine dependence, admitted to a psychiatric centre in Taiwan from January 1990 to December 2007, was retrospectively studied. Diagnostic and sociodemographic data for each subject were extracted from the medical records based on a chart review process. Mortality data were obtained by linking to the National Death Certification System and standardised mortality ratios (SMRs) were estimated. The risk and protective factors for all-cause deaths were explored by means of survival analyses.nnnRESULTSnDuring the study period, 130 patients died. Of them, 63.1% died unnatural deaths, while the remaining 36.9% died natural deaths. The 1 year cumulative rates for unnatural and natural deaths were 0.018 and 0.006, respectively, and the 5 year rates were 0.046 and 0.023, respectively. The cohort had excessive mortality (SMR = 6.02), and women had a higher SMR for unnatural deaths than men (26.19 vs. 9.82, P = 0.001). For all-cause deaths, comorbidity with other substance use disorders was associated with increased risk of death, despite that being married was associated with a reduced risk.nnnDISCUSSION AND CONCLUSIONSnA substantial proportion of the deceased died natural deaths, but most died unnatural deaths. The findings show significant evidence to provide valuable insight into premature deaths among methamphetamine-dependent users. This information is valuable for development of prevention and intervention programs.

Risk and protective factors for suicide among patients with methamphetamine dependence: A nested case-control study

OBJECTIVEnMethamphetamine as a recreational drug has undergone cycles of popularity, with a recent surge worldwide since the 1990s. This study aimed to identify clinical characteristics associated with suicide mortality in patients with methamphetamine dependence by means of a nested case-control design.nnnMETHODnIn a consecutive series of 1,480 inpatients with methamphetamine dependence (diagnosed according to DSM-III-R and DSM-IV criteria) admitted to a psychiatric center in northern Taiwan from January 1, 1990, through December 31, 2006, 38 deaths due to suicide were identified as cases via record linkage, and 76 controls were randomly selected using risk-set density sampling in a 2:1 ratio, matched for age, sex, and the year of index admission. A standardized chart review process was adopted to collate sociodemographic and clinical information for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of suicide among these patients.nnnRESULTSnFor the sociodemographic and symptom profiles at the latest admission, financial independence lowered the risk for suicide (adjusted risk ratio [ARR] = 0.33, P < .05), whereas visual hallucinations elevated the risk (ARR = 2.57, P < .05) for suicide. For the profiles during the postdischarge period, financial independence (ARR = 0.11, P < .05) remained associated with reduced risk for suicide, whereas suicide attempt (ARR = 8.78, P < .05) and depressive syndrome (ARR = 3.28, P = .059) were associated with increased risk of suicide.nnnCONCLUSIONSnBoth protective and risk factors for suicide mortality were found among inpatients with methamphetamine dependence, and the findings have implications for clinical intervention and prevention.

Psychiatric discharge against medical advice is a risk factor for suicide but not for other causes of death

To the Editor: Discharge against medical advice (DAMA) is common among psychiatric inpatients. A comprehensive review reported that the estimated prevalence ranged from 3% to 51% and increased over time.1 DAMA has received little attention in the medical literature, and most works were published a decade ago. The literature shows that patients requesting DAMA have poorer long-term prognoses,1 have greater rehospitalization rates, overuse emergency care, and underuse outpatient services. Nonetheless, regarding the outcome of suicide mortality and other causes of death, few evidence-based data2,3 have been published. To estimate the risks of DAMA on various causes of death is important for implementing effective postdischarge care. We investigated the association between DAMA and suicide as well as other causes of death by following a large cohort of psychiatric inpatients. We found that DAMA was associated with a significantly higher risk of suicide compared to nonsuicide mortality.

Protective and risk factors for inpatient suicides: A nested case–control study

This study aimed at estimating the protective effect of suicide precautions and clinical risk factors for inpatient suicides. A standardized precaution system was implemented in a large psychiatric center on January 1, 1996. A consecutive series of 33,121 admissions from 1998 to 2008 constituted the post-implementation cohort and 13,515 admissions from 1985 to 1995 constituted the pre-implementation cohort as comparison group. Inpatient suicides were identified via record linkage with national mortality database. For each of 41 inpatient suicides, four controls were randomly selected based on a nested case-control study. A standardized chart review process was employed to collate clinical information for each study subject. Risk and protective factors for inpatient suicides was estimated by conditional logistic regression. The findings showed that, among subjects with shorter lengths of stay, those admitted in post-implementation era had a significantly lower adjusted risk ratio (0.157, p=0.048) for inpatient suicides. Three depression-related symptoms elevated the risk for inpatient suicides: depressed mood (adjusted risk ratio=2.11, P=0.002), loss of energy (adjusted risk ratio=1.99, P=0.018), and psychomotor retardation (adjusted risk ratio=1.67, P=0.066; with marginal statistical significance). Suicide precautions have protective effect against inpatient suicides. A better assessment and prevention efforts is needed, particularly for those with depression-related symptoms.

Relation of genotypes of alcohol metabolizing enzymes and mortality of liver diseases in patients with alcohol dependence

The aim of this study was to investigate the relationship between alcohol metabolizing enzyme genotypes and mortality risk of liver diseases among patients with alcohol dependence. A total of 130 male patients with a DSM-III-R diagnosis of alcohol dependence (mean age 40+/-10 years) were recruited consecutively to the study from 1994 to 1995. Blood biochemistry and hepatitis B viral surface antigen (HBsAg) were measured. The genotypes of ADH2, ADH3 and ALDH2 were determined by polymerase chain reaction and restriction fragment-length polymorphism. The mortality cases were identified by matching data files of the death certification system of the National Department of Health issued from 1994 to 2001. Mortality analysis revealed that 58 of 130 cases (45%) died during the follow-up period. Among them, 21 cases died of liver diseases. Mortality was not higher in HBsAg positive than in negative subjects. The genotypes of alcohol metabolizing enzymes are not associated with the mortality risk of liver diseases. The small sample size was a limitation of this study. How functional genetic polymorphism of the alcohol metabolizing enzymes causes liver damage is still not clear. Continuous study of this topic is necessary.

Risk and protective factors for suicide mortality among patients with alcohol dependence

OBJECTIVEnPeople with alcohol dependence suffer from poor health outcomes, including excessive suicide mortality. This study estimated the suicide rate and explored the risk and protective factors for suicide in a large-scale Asian population.nnnMETHODnWe enrolled patients with alcohol dependence (ICD-9 code 303**) consecutively admitted to a psychiatric center in northern Taiwan from January 1, 1985, through December 31, 2008 (N = 2,793). Using patient linkage to the national mortality database (1985-2008), we determined that 960 patients died during the study period. Of those deaths, 65 patients died of suicide. On the basis of risk-set sampling for the selection of controls, we conducted a nested case-control study and collected the information by means of a standardized chart review process. We estimated the standardized mortality ratio (SMR) for suicide mortality. Conditional logistic regression was employed for exploring the risk and protective factors for suicide.nnnRESULTSnThe study subjects had excessive suicide and all-cause deaths, with SMRs of 21.2 and 12.7, respectively. We pinpointed auditory hallucination (adjusted risk ratio [aRR] = 1.80, P = .04) and attempted suicide (aRR = 7.52, P = .001) as the risk factors associated with suicide. In contrast, protective factors included financial independence (aRR = 0.11, P = .005) and being married (aRR = 0.16, P = .02). Intriguingly, those with physical illnesses had a lower risk of suicide (aRR = 0.15, P = .01).nnnCONCLUSIONSnCompared with the general population, those with alcohol dependence faced excessive suicide mortality. For a comprehensive approach to suicide prevention, recognizing and improving the protective factors could have equal importance in mitigating the risk of suicide.

Elevated aspartate and alanine aminotransferase levels and natural death among patients with methamphetamine dependence

Background Methamphetamine is one of the fastest growing illicit drugs worldwide, causing multiple organ damage and excessive natural deaths. The authors aimed to identify potential laboratory indices and clinical characteristics associated with natural death through a two-phase study. Methods Methamphetamine-dependent patients (nu200a=u200a1,254) admitted to a psychiatric center in Taiwan between 1990 and 2007 were linked with a national mortality database for causes of death. Forty-eight subjects died of natural causes, and were defined as the case subjects. A time-efficient sex- and age-matched nested case-control study derived from the cohort was conducted first to explore the potential factors associated with natural death through a time-consuming standardized review of medical records. Then the identified potential factors were evaluated in the whole cohort to validate the findings. Results In phase I, several potential factors associated with natural death were identified, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), comorbid alcohol use disorder, and the prescription of antipsychotic drugs. In phase II, these factors were confirmed in the whole cohort using survival analysis. For the characteristics at the latest hospital admission, Cox proportional hazards models showed that the adjusted hazard ratios for natural death were 6.75 (p<0.001) in the group with markedly elevated AST (>80 U/L) and 2.66 (p<0.05) in the group with mildly elevated AST (40–80 U/L), with reference to the control group (<40 U/L). As for ALT, the adjusted hazard ratios were 5.41 (p<0.001), and 1.44 (p>0.05). Comorbid alcohol use disorder was associated with an increased risk of natural death, whereas administration of antipsychotic drugs was not associated with lowered risk. Conclusions This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural deaths.

Antipsychotic medications and stroke in schizophrenia: A case-crossover study

Background The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia. Methods Using a retrospective cohort of patients with schizophrenia (N = 31,976) derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010). We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug. Results Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009) within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037), and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015). Conclusions Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.