Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

Schizophrenia patients discharged on antipsychotic polypharmacy from a public psychiatric hospital in Taiwan, 2006-2021.

The aim of this study was to identify the factors associated with antipsychotic polypharmacy (APP), investigate whether APP could affect the risk of rehospitalization, and explore temporal trends in APP use. Schizophrenia patients discharged from the study hospital between 2006 and 2021 (n = 16,722) were included in the analysis. The logistic regression model was employed to determine the predictors significantly associated with APP use. Survival analysis was used to compare time to rehospitalization between APP and antipsychotic monotherapy (AMT). The temporal trend of APP use was analyzed using the Cochran-Armitage Trend test. In comparison with the patients (n = 10,909) who were discharged on AMT, those (n = 5,813) on APP were significantly more likely to be male gender, to receive LAIs, to take clozapine, to take anticholinergic agents, to have a greater number of previous hospitalizations, and to have a higher CPZ equivalent dose of antipsychotic prescription. The prescription rate of APP significantly increased from 18.4 % in 2006 to 44.9 % in 2021. Compared with AMT, APP was associated with more clozapine use, more LAI use, higher doses of antipsychotics, and an increased risk of rehospitalization. In addition, the prescription of APP continued to increase during the study period.

Fourteen-year trends in the prescribing patterns of pediatric bipolar patients discharged from two public mental hospitals in Taiwan.

INTRODUCTION: The management of pediatric bipolar disorder (PBD) requires pharmacotherapy to control acute symptoms, reduce relapse, prevent suicide, and improve psychosocial functioning. The purpose of this study was to investigate prescribing patterns among PBD patients discharged from two public mental hospitals in Taiwan, from 2006 to 2019. METHODS: PBD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n = 420), were included in the analysis. Prescribed drugs at discharge, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second- and first-generation antipsychotics, SGAs and FGAs), and antidepressants, were explored. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Time trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. RESULTS: The most commonly prescribed psychotropic agents were SGAs (76.0%), followed by valproate (65.7%) and FGAs (24.8%). The prescription rates of SGAs, antidepressants, antidepressant plus antipsychotic, and antidepressant without mood stabilizer significantly increased over time, whereas the prescription rates of mood stabilizers, lithium, and FGAs significantly decreased. DISCUSSIONS: Prescribing patterns changed greatly for PBD patients over time. However, much more evidence supporting the effectiveness of psychotropic agents in PBD patients is required.

Prescribing changes for bipolar patients discharged from two public psychiatric hospitals in Taiwan, 2006-2019.

BACKGROUND: For bipolar disorder, a severe, recurring mental disorder, pharmacotherapy is a cornerstone of effective treatment. The purpose of this study was to investigate prescribing changes among patients with bipolar disorder discharged from two public psychiatric hospitals in Taiwan over a 14-year period. METHODS: Patients with bipolar disorder discharged from the two study hospitals between 2006 and 2019 (n = 9071) were included in the analysis. Prescribed drugs for the treatment of bipolar disorder, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), any antipsychotics (i.e., second- and first-generation antipsychotics; SGAs & FGAs), and any antidepressants, were examined. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. RESULTS: The prescription rates of SGAs, any antidepressants, antidepressant monotherapy, antidepressants without mood stabilizers, and complex polypharmacy significantly increased over time, whereas the prescription rates of any mood stabilizers, lithium, carbamazepine, FGAs, and antidepressants plus mood stabilizers significantly decreased. LIMITATIONS: Treatment allocation is not randomized in a retrospective study. The diagnoses of bipolar disorder were based on clinical judgments. This was a hospital-based study. CONCLUSIONS: Substantial prescribing changes took place during the study period. The decreased use of lithium and the increased use of antidepressants were not in accordance with the evidence-based treatment and recommendations in treatment guidelines. Therefore, long-term outcomes of prescribing changes should be explored in the future.

The relation between second-generation antipsychotics and laxative use in elderly patients with schizophrenia.

BACKGROUND: We aimed to investigate factors associated with concomitant laxative use among elderly patients with schizophrenia, discharged on second-generation antipsychotics (SGAs), from two large public psychiatric hospitals in Taiwan. METHODS: Elderly patients with schizophrenia who were discharged between 2006 and 2019 and received SGA monotherapy at discharge were included in the analysis. Multivariate logistic regression was used to identify factors associated with regular laxative use at discharge. The Cochrane-Armitage trend test was used to evaluate whether significant time trends existed for rates of laxative use at discharge. RESULTS: A total of 2591 elderly patients with schizophrenia were discharged during the study period, and 1727 of 2591 patients who met the inclusion criteria were included for analysis. Of these 1727 patients, 732 (42.4%) also received concomitant laxatives. Female gender, mood stabiliser use and concomitant diabetes mellitus were found to be associated with increased laxative use. Among SGAs, clozapine was associated with the highest rate of laxative use, followed by zotepine, quetiapine, olanzapine and risperidone. Additionally, risperidone, amisulpride, aripiprazole, paliperidone and sulpiride were associated with comparable rates of laxative use. Laxative use rates grew over time from 30.8% in 2006 to 46.6% in 2019 (z = 4.83, P < 0.001). CONCLUSIONS: Laxative use is common in elderly schizophrenia patients treated with SGAs. In cases of clinically significant constipation, switching to an SGA with a lower risk for constipation, or discontinuing the use of mood stabilisers should be considered, if clinically feasible.

Comparative Effectiveness of Antipsychotics in Preventing Readmission for First-Admission Schizophrenia Patients in National Cohorts From 2001 to 2017 in Taiwan.

BACKGROUND AND HYPOTHESIS: Antipsychotics remain the main treatment for schizophrenia, but their effectiveness is challenging to compare. We aimed to assess the comparative real-world effectiveness of antipsychotics in preventing readmission among patients in Asia with early-stage schizophrenia to inform clinical decision making. STUDY DESIGN: We did a retrospective cohort study of first-admission schizophrenia patients (ICD-9-CM: 295; ICD-10-CM: F20 and F25) from January 1, 2001, to December 31, 2017. The cohort was identified from the National Health Insurance Research Database NHIRD for Psychiatric Inpatients. The exposure was any antipsychotics prescribed post-discharge. The primary outcome was the readmission risk due to psychotic disorders, which was measured by adjusted hazard ratios (aHRs). Within-individual extended Cox models were applied for analyses, where the periods of oral risperidone use served as his or her own control. STUDY RESULTS: We selected 75 986 patients (men, 53.4%; mean [SD] age, 37.6 [12.0] years; mean [SD] duration of follow-up, 8.9 [5.0]) who were first admitted to psychiatric wards with schizophrenia in Taiwan. Among them, 47 150 patients (62.05%) had at least one readmission within 4 years. Compared to the period under treatment with oral risperidone, that under monotherapy with long-acting injectable antipsychotics (LAIs) had the lowest risk for psychotic readmission, with a risk reduction of 15-20%. However, the prevalence of person-prescription prevalence of LAIs remained low (< 10%) during the follow-up period. CONCLUSIONS: The use of LAIs after the first admission for schizophrenia has notable advantages in preventing readmission. Such formulations should be offered earlier in the course of illness.

Antipsychotic prescription patterns and associated factors among the elderly with psychiatric illnesses.

Prescribing rate of antipsychotics in elderly patients with psychiatric illnesses has been increasing all over the world. However, there is a lack of research examining the use of antipsychotics at psychiatric hospitals. We aim to find out long-term trends in antipsychotic prescriptions and factors associated with the use of antipsychotics in the elderly population. All outpatient visits with patients aged over 65 years between 2006 and 2015 in a psychiatric hospital were included in the analysis. Demographic and clinical data, including patient age, sex, National Health Insurance status, psychiatric diagnosis and antipsychotic prescription, were retrieved through the electronic medical information system. In this study, we found that prescribing rate of antipsychotics has increased around 5.07% through the study period (from 57.25% in 2006 to 60.15% in 2015, P < 0.001). Among all antipsychotics, there was an increase in the use of second-generation antipsychotics with a simultaneous decline in the use of first-generation antipsychotics. Logistic regression analysis showed advanced age, female gender and certification for catastrophic illnesses were positively associated with the use of antipsychotics. Furthermore, patients most likely to be prescribed an antipsychotic were those with psychotic disorders, followed by dementia, and then affective or neurotic disorders. The results of this study were consistent with the worldwide trend of increasing prescriptions of second-generation antipsychotics among elderly patients with psychiatric illnesses. Despite the potential benefits of these medications on certain psychiatric symptoms, clinicians need to exercise due caution as they may also cause potentially serious side effects among the elderly population.

Time to rehospitalization in involuntarily hospitalized individuals suffering from schizophrenia discharged on long-acting injectable antipsychotics or oral antipsychotics.

Background: Involuntarily hospitalized individuals suffering from schizophrenia often have a poorer prognosis after discharge. Objective: This study aimed to analyze time to rehospitalization within 6 months of discharge in involuntarily hospitalized individuals suffering from schizophrenia discharged on long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs). In addition, temporal trends in LAI use at discharge were explored. Methods: Involuntarily hospitalized individuals suffering from schizophrenia discharged from the study hospital between 2006 and 2019 (n = 806) were included in the analysis. Survival analysis was used to compare time to rehospitalization within 6 months of discharge between individuals discharged on LAIs and OAPs, and between first-generation antipsychotic (FGA) LAIs and second-generation antipsychotic (SGA) LAIs. The Cochran-Armitage trend test was used to test whether a temporal trend existed for LAIs use at discharge during the study period. Results: The LAIs group (n = 231) had a significantly lower rate of rehospitalization and a significantly longer time to rehospitalization than the OAPs group (n = 575). Rehospitalization rate and time to rehospitalization were not significantly different between individuals discharged on FGA-LAIs and SGA-LAIs. LAIs use at discharge grew significantly from 16.77% in 2006 to 50.00% in 2019 (Z = 6.81, p < 0.0001). Among all LAIs, only use of SGA-LAIs at discharge increased significantly (Z = 5.74, p < 0.0001), but not FGA-LAIs. Conclusions: LAIs were superior to OAPs in preventing rehospitalization. However, SGA-LAIs were comparable with FGA-LAIs in reducing rehospitalization risk. Use of LAIs increased significantly in discharged involuntarily hospitalized individuals during the study period, especially SGA-LAIs.

Identifying dopamine supersensitivity through a randomized controlled study of switching to aripiprazole from other antipsychotic agents in patients with schizophrenia.

BACKGROUND: Aripiprazole has been reported to worsen psychotic symptoms when switching from other antipsychotics, possibly due to dopamine supersensitivity psychosis. OBJECTIVE: This study aimed to explore the predictors and possible underlying mechanisms of aripiprazole-related psychotic exacerbation. METHODS: We conducted an 8-week, open-label, randomized controlled study from October 2007 to September 2009, assigning patients with a primary diagnosis of schizophrenia or schizoaffective disorder to switch from other antipsychotics to aripiprazole with 2-week dual administration, and then to taper off the original agents in fast (n = 38, within 1 week) or slow (n = 41, within 4 weeks) strategies. Positive and Negative Syndrome Scale (PANSS) was examined at day 0, 7, 14, 28, 56. Aripiprazole-related exacerbation (ARE) was defined positive as a 2-point increase in delusion/hallucination dimension score within 28 days compared with baseline. Baseline demographic, clinical and intervention-related variables were compared between the ARE+ and ARE- groups. RESULTS: Of the 79 randomized patients, 21 fulfilled the criteria of ARE+ , and 46 were classified as ARE-. Fourteen patients in the ARE+ group had worsening psychotic symptoms in the first and second weeks. Compared with the ARE- group, the ARE+ group had a higher baseline chlorpromazine equivalent dose (405.8 ± 225.8 mg vs 268.1 ± 165.4 mg, p = 0.007) and was associated with prescription of first-generation antipsychotics (p = 0.038). CONCLUSIONS: A higher dose of original antipsychotics and prescription of first-generation antipsychotics may be associated with a higher risk of ARE. The underlying mechanism might be covert dopamine supersensitivity psychosis. These findings may help to identify high-risk patients and guide appropriate treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT00545467.

Time to Rehospitalization for Different Oral Risperidone Dosing Frequencies in Patients With Schizophrenia: A 17-Year Retrospective Cohort Study.

PURPOSE: This retrospective cohort study aimed at determining whether the daily administration pattern of risperidone influences time to rehospitalization in patients with schizophrenia. Previous studies have related more frequent dosing to poor medication adherence. This causes suboptimal disease control, which entails shorter times between hospital admissions. METHODS: We investigated admission records from 1 tertiary psychiatric hospital in Taiwan. Patients were included if they had a main diagnosis of schizophrenia or schizoaffective disorder and were receiving oral risperidone. The enrollment period was July 2001 to December 2016; we observed whether rehospitalization would occur in subsequent periods of 3-month, 6-month, and 1-year follow-ups. RESULTS: There were 1504 patients grouped by daily dosing frequency of oral risperidone. Most patients (95.9%) received 6 mg or less of risperidone per day. After adjustment for covariates, including daily total dosages of risperidone, it showed an independent association that more frequent dosing frequency of risperidone had higher hazard ratios (HRs) of rehospitalizations (in 1-year follow-up: 2 vs 1 dosing a day: HR, 1.566; 3 vs 1 dosing a day: HR, 3.010; 4 vs 1 dosing a day: HR, 4.305) and a significant trend of more possible rehospitalizations (Cochran-Armitage test for trend: P < 0.001) in 3-month, 6-month, and 1-year follow-up. CONCLUSIONS: Patients receiving more doses of risperidone per day are more likely to be readmitted within 1 year following last discharge, indicating poorer treatment outcomes for patients who receive more frequent doses.

Hashimoto's encephalopathy presenting as catatonia in a bipolar patient.

Hashimoto's encephalopathy is a rare autoimmune disease the presentation of which can include a variety of neurological signs and psychiatric symptoms. Here we present a 53-year-old woman with a history of bipolar disorder who experienced catatonia, consciousness disturbance, and general weakness after the aggravation of symptoms depression. After laboratory data revealed increased blood anti-thyroid peroxidase antibodies, the patient was diagnosed as having Hashimoto's encephalopathy, and her neuropsychiatric symptoms resolved soon after she received steroid pulse therapy. Hashimoto's encephalopathy rarely presents as catatonia, but the symptoms might mimic the manifestation of a previous mental illness. Clinicians should therefore consider Hashimoto's encephalopathy an underlying cause of catatonia.

Relationship between choice of opioid agonist therapy and distance from patients' residences in Taiwan, 2012-2014.

BACKGROUND: Choice of opioid agonist therapy (OAT) for opioid use disorder (OUD) can be impacted by variables such as age, sex, and socioeconomic status. However, it remains unknown whether accessibility of treatment affects patient choice of OAT. OBJECTIVES: To investigate the association between distance to the treatment site and choice of OAT. METHODS: Electronic records were collected for the last outpatient visits of individuals with OUD between January 1, 2012 and December 31, 2014. The address of each patient was processed using the Geographic Information System to obtain the distance between place of residence and the hospital. Multivariate logistic regression was used to assess the correlation between individual drug selection and distance of residence. Among the study population of 2804 patients (81.5% male), 74.1% were receiving methadone while 25.8% were receiving buprenorphine. The vast majority (95%) of all patients lived within 50 km of the hospital, so regression analysis was limited to this distance. Sensitivity analysis was estimated using robust Poisson regression. RESULTS: Logistic regression revealed that every 1-km increase in distance from home to hospital increased the odds ratio of choosing sublingual buprenorphine tablets over methadone by 1.05 (p = .02, 95% confidence interval (CI) = 1.02-1.08). CONCLUSIONS: Patients living closer to the treatment center were more likely to choose methadone as treatment, while patients living farther away were more likely to choose sublingual buprenorphine tablets. To mitigate the influence of travel distance on therapy choice, we recommend that more medical institutions participate in OAT services.

Factors associated with laxative use in schizophrenia patients treated with second-generation antipsychotics.

The aim of this study was to investigate factors associated with concomitant laxative use among schizophrenia patients discharged on second-generation antipsychotics (SGAs) at two large psychiatric hospitals in Taiwan. Patients with schizophrenia who were discharged between 2006 and 2017 and received SGA monotherapy at discharge were included in the analysis. Multivariate logistic regression was used to identify factors associated with regular laxative use at discharge. Multivariate Cox regression was used to determine the effect of laxative use at discharge on time to rehospitalization within one year. The Cochran-Armitage trend test was used to evaluate whether significant time trends existed for rates of laxative use at discharge during the study period. Among patients discharged on SGAs (n = 11,861), 3,336 (28.1%) also received concomitant laxatives. Advanced age and higher antipsychotic or anticholinergic doses were found to be associated with an increase in laxative use. Among SGAs, clozapine was associated with the highest rate of laxative use, followed by zotepine, quetiapine, olanzapine and risperidone. Additionally, risperidone, amisulpride, aripiprazole, paliperidone and ziprasidone were associated with comparable rates of laxative use. In contrast, sulpiride was least associated with laxative use among all SGAs. Regular laxative use at discharge was found to be significantly associated with psychiatric rehospitalization. Also, rate of laxative use at discharge increased significantly during the study period. Laxative use is common in schizophrenia patients treated with SGAs. For clinically significant constipation, switching to an SGA with a lower risk for constipation, and decreasing the doses of SGAs and anticholinergics should be considered.

Longitudinal factors associated with mortality in older patients with mood disorders.

BACKGROUND: To clarify the longitudinal risk factors for mortality in older people with bipolar disorder (BD) and major depressive disorder (MDD). METHODS: This study is a national cohort study of older patients with mood disorders. Patients were identified from Taiwan's National Health Insurance Research Database and followed from 2008 to 2011. We determined the mortality rates and standardized mortality ratios (SMRs) in this study population. Survival analyses were conducted to examine factors and healthcare utilization patterns associated with mortality during the 3-year follow-up period. RESULTS: 26,570 patients aged ≥ 65 years and diagnosed with and treated for BD or MDD in 2008 were enrolled (5,854 and 20,716 with BD and MDD, respectively). Within the 3-year follow-up period, 15.24% (n=4048) of the enrolled patients died, including 1003 (17.13%) in the BD and 3045 (14.70%) in the MDD groups. The SMRs for BD and MDD were 1.65 (1.56-1.76), and 1.26 (1.21-1.32), respectively. Among the examined comorbidities, dementia, diabetes mellitus and renal diseases each constituted an elevated relative mortality risk. By contrast, hypertension and hyperlipidemia were associated with a lower risk of mortality. LIMITATION: In Taiwan's National Health Insurance program, specific medications are prescribed for specific diagnoses and confounding by indication should be kept in mind. CONCLUSION: Older patients with mood disorders had a relatively high mortality risk over the 3-year follow-up period. Early detection, risk prevention, and better management of comorbid physical and mental disorders can improve the health outcomes of older patients with BD and MDD.

Time to rehospitalization in patients with bipolar mania discharged on long-acting injectable or oral antipsychotics.

OBJECTIVE: This study aimed to analyze time to rehospitalization in patients with bipolar mania discharged on long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs). Additionally, temporal trends in LAI prescription were investigated. METHODS: Patients with bipolar mania discharged from the study hospital on antipsychotics between 2006 and 2018 were included. Survival analysis was used to compare time to rehospitalization within one year of discharge between patients discharged on LAIs and OAPs, and between FGA-LAIs (first- generation antipsychotic) and SGA-LAIs (second-generation antipsychotic). The Cochrane-Armitage trend test was used to test whether a temporal trend existed for LAI prescription rates during the study period. RESULTS: The LAI group (n = 224) had a significantly lower rehospitalization rate and a significantly longer time to rehospitalization than the OAP group (n = 3836). Rehospitalization rate and time to rehospitalization were not significantly different between patients discharged on FGA-LAIs or SGA-LAIs. The LAI prescription rate grew significantly from 2.20% in 2006 to 11.58% in 2018 (Z = 5.5843, p < 0.0001). The prescription rate of SGA-LAIs also increased significantly (Z = 7.7141, p < 0.0001), but not the prescription rate of FGA-LAIs. LIMITATIONS: The treatment allocation is not randomized in this retrospective study. Furthermore, various clinical characteristics were unavailable in our analysis, such as symptom severity, functional impairment, and others. CONCLUSIONS: LAIs were significantly superior to OAPs in reducing rehospitalization risk. However, SGA-LAIs were comparable with FGA-LAIs in reducing rehospitalization risk. Use of LAIs increased significantly in discharged patients with bipolar disorder during the study period, especially SGA-LAIs.

Abnormally low prolactin levels in schizophrenia patients after switching to aripiprazole in a randomized trial: a biomarker for rebound in psychotic symptoms?

BACKGROUND: Switching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hyperprolactinemia but may result in an abnormally low prolactin level. This study aimed to assess whether the aripiprazole-induced abnormally low prolactin level was a biomarker for subsequent rebound of positive symptoms in schizophrenia patients. METHODS: Participants were 63 patients in an 8-week trial of switching to aripiprazole, in which preswitching antipsychotics were maintained for the first 2 weeks and aripiprazole was fixed at 15 mg orally throughout the trial. A prolactin level of < 3.7 ng/ml was defined as abnormally low, and an increase of two or more points in the positive subscore of the Positive and Negative Syndrome Scale at two adjacent ratings was defined as a psychotic rebound. RESULTS: Among 63 patients, 25 (39.7%) had an abnormally low prolactin level and 21 (33.3%) had a psychotic rebound after switching to aripiprazole. In patients with abnormally low prolactin levels, 48.0% of them had a rebound in psychotic symptoms, whereas in those without abnormally low prolactin levels 23.7% did so. Multivariable logistic regression analysis with adjustment for sex, early age at onset, and preswitching medications revealed that abnormally low prolactin levels were associated with psychotic rebound (adjusted odds ratio = 3.55, 95% confidence interval = 1.02, 12.5). Furthermore, there was concurrency between the trend of the cumulative proportion of patients having an abnormally low prolactin level and that of the cumulative proportion of patients having a rebound in psychotic symptoms. CONCLUSIONS: An abnormally low prolactin level after switching to aripiprazole in schizophrenia patients was a potential warning sign of a psychotic rebound. Hence, monitoring of prolactin levels after switching to aripiprazole may help avoid such rebound in schizophrenia. TRIAL REGISTRATION: NCT00545467 ; Date of registration: 17/10/2007.

Temporal trends in clozapine use at time of discharge among people with schizophrenia at two public psychiatric hospitals in Taiwan, 2006-2017.

Clozapine treatment remains the gold standard for treatment-resistant schizophrenia. This study aimed to describe temporal trends in clozapine use at discharge among patients with schizophrenia at two of the largest public psychiatric hospitals in Taiwan over a twelve-year period. Patients with schizophrenia discharged from the two study hospitals between 2006 and 2017 (n = 24,101) were included in the analysis. Antipsychotic augmentation was defined as concomitant use of a second antipsychotic as augmentation to clozapine treatment. Changes in the rate of clozapine use and antipsychotic augmentation at discharge over time were analyzed using the Cochran-Armitage trend test. Patients discharged on clozapine had significantly longer hospital stays than other patients. The rate of clozapine use at discharge increased from 13.8% to 20.0% over time (Z = 6.88, p < .0001). Concomitant use of anticholinergic medication was more common in patients receiving antipsychotic augmentation than clozapine antipsychotic monotherapy. Among patients discharged on clozapine, the rate of augmentation with a second antipsychotic increased from 19.1% to 36.2% over time (Z = 6.58, p < .0001). Among patients receiving antipsychotic augmentation, use of another second-generation antipsychotic as the augmentation agent grew from 32.6% to 65.5% over time (Z = 8.90, p < .0001). The increase in clozapine use was accompanied by an increase in concomitant use of a second antipsychotic as augmentation during the study period. Further studies are warranted to clarify the risk/benefit of this augmentation strategy. Clozapine may still be underutilized, and educational programs are needed to promote clinical use of clozapine.

Excess mortality and shortened life expectancy in people with major mental illnesses in Taiwan.

AIMS: Given the concerns of health inequality associated with mental illnesses, we aimed to reveal the extent of which general mortality and life expectancy at birth in people with schizophrenia, bipolar disorder and depressive disorder varied in the 2005 and 2010 nationally representative cohorts in Taiwan. METHODS: Two nationally representative samples of individuals with schizophrenia, bipolar disorder and depressive disorder were identified from Taiwan's national health insurance database in 2005 and 2010, respectively, and followed-up for consecutive 3 years. The database was linked to nationwide mortality registry to identify causes and date of death. Age-, gender- and cause-specific mortality rates were generated, with the average follow-up period of each age- and gender-band applied as 'weighting' for the calculation of expected number of deaths. Age- and gender-standardised mortality ratios (SMRs) were calculated for these 3-year observation periods with Taiwanese general population in 2011/2012 as the standard population. The SMR calculations were then stratified by natural/unnatural causes and major groups of death. Corresponding life expectancies at birth were also calculated by gender, diagnosis of mental disorders and year of cohorts for further elucidation. RESULTS: The general differential in mortality rates for people with schizophrenia and bipolar disorder remained wide, revealing an SMR of 3.65 (95% confidence interval (CI): 3.55-3.76) for cohort 2005 and 3.27 (3.18-3.36) for cohort 2010 in schizophrenia, and 2.65 (95% CI: 2.55-2.76) for cohort 2005 and 2.39 (2.31-2.48) for cohort 2010 in bipolar disorder, respectively. The SMRs in people with depression were 1.83 (95% CI: 1.81-1.86) for cohort 2005 and 1.59 (1.57-1.61) for cohort 2010. SMRs due to unnatural causes tended to decrease in people with major mental illnesses over the years, but those due to natural causes remained relatively stable. The life expectancies at birth for schizophrenia, bipolar disorder and depression were all significantly lower than the national norms, specifically showing 14.97-15.50 years of life lost for men and 15.15-15.48 years for women in people with schizophrenia. CONCLUSIONS: Compared to general population, the differential in mortality rates for people with major mental illnesses persisted substantial. The differential in mortality for unnatural causes of death seemed decreasing over the years, but that due to natural causes remained relatively steady. Regardless of gender, people with schizophrenia, bipolar disorder and depression were shown to have shortened life expectancies compared to general population.

Factors Affecting Changes of Cluster of Differentiation 4 Cell Counts Among Human Immunodeficiency Virus-positive People Who Inject Heroin and Receive Methadone Maintenance Treatment.

AIMS: Opioids have been hypothesized to suppress the immune function and worsen outcomes among people living with human immunodeficiency virus (HIV). The study aimed to identify key factors associated with the increased cluster of differentiation 4 (CD4) cell counts among HIV-positive people who inject heroin and receive methadone maintenance treatment (MMT). METHODS: This longitudinal study was conducted at a psychiatric hospital in Northern Taiwan. Participants were recruited from 2006 through 2011, and received CD4 cell counts and HIV viral load monitoring once every 4 to 6 months. Trend in CD4 cell counts, defined as change in CD4 cell count over time, was used as the outcome measure. Independent variables included MMT-related factors and baseline characteristics. Baseline characteristics included age, gender, CD4 cell count, HIV viral load, tests for other infections, liver function tests, and urine drug screens. RESULTS: Three hundred and fifty one participants were recruited during the study period. The multivariate linear mixed model analysis revealed a higher MMT attendance rate, a higher baseline CD4 cell count, and a shorter duration of MMT were associated with an increase in CD4 cell count over time. CONCLUSIONS: The study showed better adherence to MMT was associated with better preserved immune functions. The negative impact of duration of MMT on CD4 cell counts may be ameliorated by improving the attendance rate, initiation of MMT earlier when the baseline CD4 cell count is still relatively high and by the other beneficial effects of MMT, such as healthier lifestyles with reduced use of short-acting opioids.

Nicotine Replacement Therapy and Healthy Lifestyle Psychoeducation for Smoking Reduction in Acute Psychiatric Inpatients: A Cluster-Randomized Parallel Study.

BACKGROUND: Effectiveness of nicotine replacement therapies in acute psychiatric inpatient settings remains under-researched. The aim of this study was to compare effectiveness and acceptability of 3 different forms of nicotine replacement therapy in achieving smoking reduction among acute psychiatric inpatients. METHODS: This cluster-randomized, parallel study compared effectiveness and acceptability of nicotine inhalers, nicotine gum, and nicotine patches for smoking reduction in the acute psychiatric inpatient setting. The primary outcome was the exhaled breath carbon monoxide (CO) level change from baseline at weeks 4 and 8. Secondary outcomes included changes in nicotine withdrawal symptoms and psychiatric symptom severity. RESULTS: Three hundred ten inpatients on the acute care wards were randomly assigned to nicotine inhalers (n = 184), gum (n = 71), and patches (n = 55). Only the nicotine inhaler group showed statistically significant reduction in CO level from baseline at both weeks 4 and 8 (P < 0.001 and P = 0.032, respectively). The nicotine inhaler and the patch group showed significant decrease in nicotine withdrawal symptoms from baseline at both weeks 4 and 8. Meanwhile, the nicotine inhaler and the gum group showed significant decrease in psychiatric symptom severity from baseline at both weeks 4 and 8. Post hoc comparisons revealed that the inhaler group had a greater decrease in psychiatric symptom severity compared with the patch group. CONCLUSIONS: Nicotine inhalers may be an effective choice for smoking reduction in acute psychiatric inpatient settings given its significant effects on CO level, withdrawal symptoms, and psychiatric symptom severity, particularly during the first 4 weeks of treatment.