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.

Unfavorable cancer mortality-to-incidence ratios in patients with schizophrenia: A nationwide cohort study in Taiwan, 2000-2019.

OBJECTIVES: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality-to-incidence ratio (MIR), which is rare in the literature. METHODS: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population. RESULTS: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92-0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23-1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30-1.42). CONCLUSION: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities.

Healthcare utilization and comorbidity shortly before suicide mortality in patients with attention-deficit/hyperactivity disorder: a nested case-control study.

BACKGROUND: Few studies have analyzed healthcare utilization before suicide among individuals with attention-deficit/hyperactivity disorder (ADHD). This study examined the pattern of healthcare utilization and comorbidities shortly before death among patients with ADHD who died by suicide and compared these data with those of living controls. This study used Taiwan's National Health Insurance Research Database to identify patients with ADHD (N = 379,440) between January 1, 2001, and December 31, 2016. Subsequently, the researchers identified 159 suicide decedents by linking each patient with the National Mortality Database. By conducting a nested case-control study with risk-set sampling from the ADHD cohort, the researchers selected 20 age- and sex-matched controls (n = 3180) for each patient who died by suicide (cases). The researchers then applied conditional logistic regression to investigate differences in healthcare utilization as well as psychiatric and physical comorbidities between case patients and controls. Case patients had higher healthcare utilization within 3 months before suicide, particularly in the psychiatry, emergency, internal medicine, neurosurgery, and plastic surgery departments. These patients also had higher risks of psychiatric comorbidities, including schizophrenia, bipolar disorder, depressive disorder, and sleep disorder, as well as physical comorbidities such as hypertension and other forms of heart disease. Among patients with ADHD, suicide decedents had increased healthcare utilization and higher risks of specific psychiatric and physical comorbidities than living controls. Thus, for suicide prevention among individuals with ADHD, suicide risk must be detected early and comorbidities should be adequately managed.

Healthcare utilization, psychiatric disorders, and physical illnesses shortly before suicide mortality in adolescents in Taiwan.

BACKGROUND: This study examined the pattern of medical utilization and the distribution of comorbidities shortly before death among adolescents who died from suicide and compared these data with those of living controls. METHODS: From Taiwan's National Health Insurance Research Database, this study identified adolescents aged 10-19 years who died from suicide (n = 935) between 1 January 2000, and 31 December 2016, by linking each patient with the national mortality database. The researchers conducted a nested case-control study through risk set sampling, and for each case, 20 age- and sex-matched controls (n = 18 700) were selected from the general population. The researchers applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls. RESULTS: Cases had a higher proportion of contact with the psychiatric department but a similar proportion of contact with any non-psychiatric medical department within 1 year before suicide compared with controls. There were 18.6% of adolescent suicide victims who only had contacted with a psychiatric department 3 months before suicide. Moreover, cases had a higher proportion of contact with non-psychiatric services within 3 months before suicide, particularly with emergency, surgery, and internal medicine departments. Cases had higher risks of several psychiatric disorders and physical illnesses, including heart diseases, pneumonia, and ulcer disease, than did controls. CONCLUSIONS: The findings of increased medical utilization and higher risks of physical and psychiatric comorbidities in adolescent suicide victims are crucial for developing specific interventions to prevent suicide in this population.

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.

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.

Excess incidence and risk factors for recurrent pneumonia in bipolar disorder.

AIM: Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD. METHODS: In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk-set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs. RESULTS: The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person-years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first- and second-generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence. CONCLUSION: We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre-existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia.

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.

Excessive suicide mortality and risk factors for suicide among patients with heroin dependence.

BACKGROUND: The mortality risk is high among individuals dependent on heroin, and suicide is a severe consequence of long-term heroin use. We estimated the incidence of suicide mortality and its risk factors in a large Asian cohort with heroin dependence. METHODS: A consecutive series of 2750 inpatients dependent on heroin admitted to a psychiatric center in northern Taiwan between 1990 and 2010 were retrospectively enrolled as the study cohort. These patients were linked to the Taiwan National Mortality Database to obtain each mortality event. We determined the Standardized Mortality Ratio (SMR) for each cause of death. Among the deceased, 69 deaths were due to suicide (cases); 138 controls were randomly selected using risk-set density sampling based on a nested case-control design. We collected clinical information from subjects' medical records. Multivariate conditional logistic regression was employed to explore the correlates of suicide mortality. RESULTS: The findings showed a 7.9-fold SMR for all-cause mortality among heroin users compared to the general population while the SMR for suicide mortality was 16.2. Multivariate analysis showed that suicide attempt as the reason for the index admission (adjusted risk ratio [RR] = 4.29, p = 0.035) and depressive syndrome anytime during life (adjusted RR = 2.61, p = 0.019) were associated with the risk of suicide mortality. CONCLUSIONS: Individuals dependent on heroin are more likely to die of suicide compared to the general population. We recommend that clinical psychiatric staff carefully gather information related to the identified risk factors to prevent suicide among heroin users.

A double-blind, placebo-controlled trial of dextromethorphan combined with clonidine in the treatment of heroin withdrawal.

Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in both animal and human subjects. In the present study, we investigated the efficacy of dextromethorphan as an add-on medication in heroin detoxification treatment in a double-blind, placebo-controlled design. Sixty-five heroin-dependent patients (male, 63; female, 2) participated in this inpatient detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a day was given as an antiwithdrawal medication at baseline. Each patient was then randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4 times a day as additional medication. Flurazepam 30 mg was given before bedtime for insomnia. Other medications that were allowed included loperamide for diarrhea and lorazepam for agitation. Participants were monitored using the Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare drug efficacy between groups. Generalized estimating equation model analysis revealed that the Objective Opioid Withdrawal Scale had no group difference between dextromethorphan and placebo group overall (P = 0.29), whereas a significant difference between groups was found during day 3 to day 6 (P = 0.04) by post hoc analysis. There was no difference in the Clinical Global Impression Scale, patient's impression of treatment, and use of ancillary medications between groups. No severe adverse effects were noticed. We suggest that dextromethorphan has some beneficial effect in attenuating the severity of opioid withdrawal symptoms and can be used as an adjunction medication in the treatment of opioid withdrawal, whereas the exact efficacy needs further investigation.

Using cognitive modelling to investigate the psychological processes of the Go/NoGo discrimination task in male abstinent heroin misusers.

AIMS: To use cognitive modelling to investigate psychological processes underlying decision-making in male abstinent heroin misusers (AHMs). DESIGN: A case-control study design. SETTING: A drug misuse treatment centre in Taiwan. PARTICIPANTS: Eighty-eight male AHMs and 48 male controls. MEASUREMENTS: Four parameters representing the attention to wins, learning rate, response sensitivity and incentive of heroin-related stimuli from the modified Go/NoGo discrimination task. FINDINGS: A modified cue-dependent learning (CD) model with four parameters representing attention to wins, learning rate, response sensitivity and incentive of heroin-related stimuli had a lower value of the sum of Bayesian information criterion (showing a better fit) than the original CD model (9555.50 versus 11,192.22, P < 0.001). The AHM group had a higher value of the heroin-incentive parameter than the control group (0.26 versus -1.66, P < 0.05). The attention to wins and heroin-incentive parameters were associated positively with total commission rate and negatively with total omission rate in the AHM group (P < 0.001). CONCLUSIONS: Male abstinent heroin misusers appear to be more influenced by heroin-related stimuli during decision-making than males with no history of heroin misuse.

Oxidative stress status in recently abstinent methamphetamine abusers.

AIM: Methamphetamine (METH) administration is associated with excessive oxidative stress. It is not known whether the systemic oxidative stress indices would alter during early abstinence in METH abusers with positive urine testing for recent METH exposure. METHODS: Sixty-four non-treatment-seeking METH abusers enrolled from a controlled environment and 60 healthy controls participated in the study. Fasting serum malondialdehyde (MDA) levels and anti-oxidant indices, including superoxide dismutase (SOD) and catalase (CAT) activity, and glutathione (GSH) levels, were measured at baseline and 2 weeks after the first measurement. We compared the differences of these oxidative stress indices between METH abusers and controls and examined the changes of the indices 2 weeks after baseline in the METH group. RESULTS: At baseline, the recently abstinent METH abusers had significantly higher MDA levels, lower SOD activity, and higher CAT activity and GSH levels compared to healthy controls. CAT and GSH values were positively correlated with MDA but negatively correlated with SOD. These oxidative stress indices did not significantly correlate with age, smoking amount, Alcohol Use Disorder Identification Test scores, or METH use variables. After 2 more weeks of abstinence, the indices did not alter nor normalize. CONCLUSION: Compared to controls, we found that METH abusers have persistently higher systemic oxidative stress throughout early abstinence. The compromised SOD as well as elevated CAT activity and GSH levels may act together as a compensatory mechanism to counteract excessive oxidative stress induced by METH. Whether the oxidative stress could improve after a longer period of abstinence needs to be examined in future studies.

Venlafaxine for acute heroin detoxification: a double-blind, randomized, control trial.

OBJECTIVES: Dissatisfaction with current available heroin detoxification regimens has led to the search for alternatives. Evidences have shown that several neurotransmission systems, including serotonin, are involved in opioid withdrawal. This study investigated the efficacy and tolerability of venlafaxine, a serotonin-norepinephrine reuptake inhibitor, in managing heroin withdrawal symptoms. METHODS: This was a randomized, double-blind, and placebo-controlled 7-day trial. Thirty-four heroin-dependent inpatients seeking detoxification were enrolled and assigned to either the venlafaxine (n = 15) or the placebo group (n = 19). The subjects received either venlafaxine 300 mg/d or placebo as their treatment regimen. Outcome measures were Objective Opioid Withdrawal Scale, total sleeping time, visual analog scale for subjective withdrawal severity, Clinical Global Impression scores on discharge, patient's impression of treatment, and amount of ancillary medications used. Data of outcome measures were analyzed by generalized estimating equation model. RESULTS: We analyzed the data from 20 subjects (8 in venlafaxine group and 12 in placebo group) who remained in the study after the fifth day of the trial. Objective Opioid Withdrawal Scale, visual analog scale, and total sleeping time demonstrated a significant efficacy of venlafaxine compared with the placebo group (P < 0.0001, P = 0.0195, and P < 0.0001, respectively). There was no difference in Clinical Global Impression and patient's impression of treatment between the 2 groups, although the placebo group needed more ancillary medications. CONCLUSIONS: Despite the small sample size, this study showed that venlafaxine is effective in alleviating withdrawal symptoms of heroin with good tolerability and safety.

Comparison of the prevalence of substance use and psychiatric disorders between government- and self-employed commercial drivers.

Five hundred and five city government-employed bus drivers (GED) and 506 self-employed drivers (SED) who were primarily taxi drivers attending annual health check-ups were studied. A two-step survey was applied. Data on basic demographics were collected, the 12-item Chinese Health Questionnaire (CHQ), Michigan Alcoholism Screening Test (MAST), Drug Abuse Screen Test (DAST) questionnaires were administered and urine drug screening for amphetamine and benzodiazepines was performed in all subjects. Subjects with MAST scores > or =3, DAST > or =5 from both groups and CHQ > or =4 for the GED group and CHQ > or =7 for the SED group were regarded as a high-risk group; and subjects with normal MAST, DAST and CHQ results serving as the comparison group were invited for further interview by psychiatric specialists using the Mini International Neuropsychiatric Interview. The mean CHQ scores were 0.94 +/- 1.53 for the GED group and 2.08 +/- 2.42 for the SED group. The mean MAST scores for the GED and SED groups were 0.23 +/- 0.58 and 0.38 +/- 1.12; and the mean DAST scores were 1.03 +/- 0.85 and 1.41 +/- 1.89, respectively. The positive rate for benzodiazepines in urine screening by enzyme immunoassay was 8.3% for the GED group, and 8.5% for the SED group. After specification using liquid chromatography, this rate reduced to 4.6% and 3.7%, respectively. Only one subject in the SED group tested positive for urine amphetamine. The SED group had a higher rate of neurotic problems, psychiatric diagnosis and a higher frequency of substance use than the GED group. These findings suggest that different work style of commercial drivers may contribute to this phenomenon. The rate of psychiatric diagnosis was significantly higher in the high-risk subjects from both groups. Questionnaires such as CHQ, DAST and MAST are useful tools to screen out subjects at high risk of psychiatric disorders during routine health checks in labor workers.