Population-attributable fraction of psychiatric and physical disorders for suicide among older adults in Taiwan.

BACKGROUND: This study aimed to estimate the population-attributable fraction (PAF) of psychiatric and physical disorders for suicide among older adults, focusing on sex- and age-specific factors. METHODS: Data from Taiwan's National Health Insurance Research Data and National Death Registry included 9136 cases of suicide in individuals aged 65+, with 89,439 matched controls. Physical and psychiatric disorders were identified through diagnostic records. Conditional logistic regression assessed risk factors, and PAF was calculated using disorder prevalence and adjusted odds ratios. RESULTS: Major suicide risk factors among older adults were depressive disorders, anxiety disorders, and sleep disorders. Physical disorders like hypertension, peptic ulcers, and cancer also showed significant PAF values. The combined PAF of physical disorders equaled that of psychiatric disorders. Psychiatric disorders had a greater impact on women and the youngest-old adults, while physical disorders had a higher contribution among men, middle-old adults, and oldest-old adults. LIMITATIONS: Relying solely on claim data to identify psychiatric and physical disorders may underestimate their prevalence and associations with suicide due to unrecorded cases of individuals not seeking help and the absence of key risk factors like social isolation and family support. CONCLUSIONS: This study identifies preventable or treatable risk factors for older adult suicide, emphasizing the need to target specific psychiatric and physical disorders in suicide prevention efforts while taking into account sex- and age-specific considerations. It also underscores the importance of establishing social welfare support systems to address the unique challenges older adults face.

Clinical outcomes, medical costs, and medication usage patterns of different somatic symptom disorders and functional somatic syndromes: a population-based study in Taiwan.

BACKGROUND: Somatic symptom disorders (SSD) and functional somatic syndromes (FSS) are often regarded as similar diagnostic constructs; however, whether they exhibit similar clinical outcomes, medical costs, and medication usage patterns has not been examined in nationwide data. Therefore, this study focused on analyzing SSD and four types of FSS (fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, functional dyspepsia). METHODS: This population-based matched cohort study utilized Taiwan's National Health Insurance (NHI) claims database to investigate the impact of SSD/FSS. The study included 2 615 477 newly diagnosed patients with SSD/FSS and matched comparisons from the NHI beneficiary registry. Healthcare utilization, mortality, medical expenditure, and medication usage were assessed as outcome measures. Statistical analysis involved Cox regression models for hazard ratios, generalized linear models for comparing differences, and adjustment for covariates. RESULTS: All SSD/FSS showed significantly higher adjusted hazard ratios for psychiatric hospitalization and all-cause hospitalization compared to the control group. All SSD/FSS exhibited significantly higher adjusted hazard ratios for suicide, and SSD was particularly high. All-cause mortality was significantly higher in all SSD/FSS. Medical costs were significantly higher for all SSD/FSS compared to controls. The usage duration of all psychiatric medications and analgesics was significantly higher in SSD/FSS compared to the control group. CONCLUSION: All SSD/FSS shared similar clinical outcomes and medical costs. The high hazard ratio for suicide in SSD deserves clinical attention.

Associations between depression and cancer risk among patients with diabetes mellitus: A population-based cohort study.

BACKGROUND: The co-occurrence of depression and diabetes mellitus has been linked to an increased risk of developing cancer. This study aimed to investigate whether depression further amplifies the risk of cancer among individuals with diabetes. METHODS: This population-based matched cohort study utilized Taiwan's National Health Insurance claims database. A total of 85,489 newly diagnosed diabetic patients with depressive disorders were selected, along with 427,445 comparison subjects. The matching process involved age, sex, and the calendar year of diabetes onset. The average follow-up duration for the two cohorts was 6.4 and 6.5 years, respectively. The primary outcome of interest was the occurrence of overall cancer or cancer at specific anatomical sites. RESULTS: The adjusted hazard ratios for overall cancer incidence were 1.08 (95% CI, 1.05-1.11). For site-specific cancers, depression exhibited significant associations with oropharyngeal, esophageal, liver, gynecological, prostate, kidney, and hematologic malignancies among patients with diabetes. Notably, a severity-response relationship was observed, indicating that patients with recurrent episodes of major depressive disorders exhibited a higher incidence of cancer compared to those diagnosed with dysthymia or depressive disorder not otherwise specified. Furthermore, the strength of the association between depression and cancer risk was more pronounced among younger patients with diabetes as opposed to older adults. However, no significant relationship was observed between adherence to antidepressant treatment and cancer risk. CONCLUSIONS: The findings of this study indicate a significant association between depression and an elevated risk of cancer among individuals diagnosed with diabetes. Future investigations should replicate our findings, explore the effects of pharmacological and non-pharmacological treatments on cancer risk, and identify the underlying mechanisms.

Associations between antenatal education program and mental health outcomes in Taiwan: A population-based cohort study.

Universal antenatal education has been offered to expectant mothers in Taiwan since 2014. Depression screening is included in the offered education sessions. This study aimed to examine the association of antennal education and depression screening with mental health outcomes, including perinatal depression diagnosis and psychiatrist visits. Data was obtained from the antenatal education records and Taiwan's National Health Insurance claims database. A total of 789,763 eligible pregnant women were included in the current study. The psychiatric-related outcomes were measured between antenatal education and the six-month after delivery. It was found that the antenatal education was widely used in Taiwan, and the attendance rate has increased to 82.6% since its launch. The attenders were more likely to be from disadvantaged backgrounds, and 5.3% of them were screened positive for depressive symptoms. They were also more likely to visit a psychiatrist but less likely to be diagnosed with depression than the non-attenders. Factors including young age, high healthcare utilization, and comorbid psychiatric disorder history were consistently associated with depression symptoms, perinatal depression diagnoses and psychiatrist visits. Further research is needed to understand the reasons for the nonattendance at antenatal education programmes and the barriers to utilizing mental health services.

Ten-year trends in depression care in Taiwan.

BACKGROUND/PURPOSE: The number of psychiatrists working in community clinics in Taiwan has increased dramatically in the recent decade. This study aimed to investigate the trend of prevalence and incidence of depressive disorders and assess the quality of depression care between 2007 and 2016 in Taiwan. METHODS: We used the claims database derived from Taiwan's National Health Insurance (NHI) program, in which approximately 23.0 million individuals were enrolled, translating to a coverage rate of 99%. Patients with depressive disorders were identified based on International Classification of Diseases codes. The process indicators of depression care quality included visit, duration, and dose adequacy. The outcome indicators included the rate of psychiatric hospitalisation, emergency visit, self-harm hospitalisation, and suicide. RESULTS: The prevalence of treated depressive disorders increased from 1.61% in 2007 to 1.92% in 2016, i.e., a 25% increase, whereas the incidence of first-ever or recurrent depressive disorder did not change significantly. The number of patients treated by psychiatrists and in community clinics also increased. The quality of depression care improved, the proportion of patients receiving minimum psychiatric clinic follow-up and adequate medication increased, and the rate of emergency visits, psychiatric hospitalisation, and self-harm hospitalisation declined. CONCLUSION: The community-based psychiatric services increased and the quality indicators of depression care in Taiwan improved during 2007-2016. The causality warrants further investigations.

Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes.

AIMS/HYPOTHESIS: Psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD), are highly comorbid with type 2 diabetes. However, the mechanisms underlying such comorbidity are understudied. This study explored the familial aggregation of common psychiatric disorders and type 2 diabetes by testing family history association, and investigated the shared genetic loading between them by testing the polygenic risk score (PRS) association. METHODS: A total of 105,184 participants were recruited from the Taiwan Biobank, and genome-wide genotyping data were available for 95,238 participants. The Psychiatric Genomics Consortium-derived PRS for SCZ, MDD and BPD was calculated. Logistic regression was used to estimate the OR with CIs between a family history of SCZ/MDD/BPD and a family history of type 2 diabetes, and between the PRS and the risk of type 2 diabetes. RESULTS: A family history of type 2 diabetes was associated with a family history of SCZ (OR 1.23, 95% CI 1.08, 1.40), MDD (OR 1.19, 95% CI 1.13, 1.26) and BPD (OR 1.26, 95% CI 1.15, 1.39). Compared with paternal type 2 diabetes, maternal type 2 diabetes was associated with a higher risk of a family history of SCZ. SCZ PRS was negatively associated with type 2 diabetes in women (OR 0.92, 95% CI 0.88, 0.97), but not in men; the effect of SCZ PRS reduced after adjusting for BMI. MDD PRS was positively associated with type 2 diabetes (OR 1.04, 95% CI 1.00, 1.07); the effect of MDD PRS reduced after adjusting for BMI or smoking. BPD PRS was not associated with type 2 diabetes. CONCLUSIONS/INTERPRETATION: The comorbidity of type 2 diabetes with psychiatric disorders may be explained by shared familial factors. The shared polygenic loading between MDD and type 2 diabetes implies not only pleiotropy but also a shared genetic aetiology for the mechanism behind the comorbidity. The negative correlation between polygenic loading for SCZ and type 2 diabetes implies the role of environmental factors.

Characteristics and psychopathology of 1,086 patients who self-poisoned using pesticides in Taiwan (2012-2019): A comparison across pesticide groups.

Background Previous studies, mainly from low- and middle-income settings, showed that pesticide self-poisonings were mostly impulsive with low levels of psychopathology. We aimed to investigate whether pesticide self-poisoning in a high-income country showed similar profiles, and whether those with certain characteristics and psychopathology were more likely to use specific pesticides. Methods Data were extracted from hospital records of pesticide self-poisoning patients treated at eight major hospitals in Taiwan between 2012 and 2019. Multinomial logistic regression was used to investigate the association of interpersonal conflicts, triggers of self-poisoning, and psychopathology with the groups of pesticides ingested. Results A total of 1,086 patients who self-poisoned using pesticides were identified; 67.0% were male and 39.8% aged 65+ years. Approximately three quarters (75.7%) of patients who received psychiatric assessment had at least one psychiatric diagnosis, and the prevalence was 48.3% in all patients. No association was found between the pesticide groups ingested and interpersonal conflicts, most of the triggers, past psychiatric service use, or having psychiatric diagnoses. Limitations Data were collected from hospital records retrospectively. Only 60.3% of the patients received a psychiatric assessment. Conclusions The majority of patients who self-poisoned using pesticides and received psychiatric assessment in Taiwan had psychiatric illness. Patients who ingested different groups of pesticides were similar in their characteristics. The choice of pesticides used in self-poisoning more likely relates to availability rather than intentional selection. Psychiatric assessment and treatment are important in patients who self-poisoned using pesticides, while restricting access to highly hazardous pesticides is likely to prevent many deaths from pesticide self-poisoning.

Psychotropic use and risk of stroke among patients with bipolar disorders: 10-year nationwide population based study.

OBJECTIVES: To investigate the association between psychotropic agents (including antipsychotics, antidepressants and mood stabilizers) and risk of stroke among patients with bipolar disorders. METHODS: We conducted a disease risk score-matched nested case-control study and identified patients with bipolar disorders (ICD-9 codes: 296.0x, 296.1x, 296.4x, 296.5x, 296.6x, 296.7x, 296.80, 296.81 or 296.89) from the National Health Insurance Research Database in Taiwan. Among them, we identified 1232 cases (981 were ischemic stroke and 251 were hemorrhagic stroke) and 5314 disease risk score-matched controls. Conditional logistic regression model equations were applied to determine the effect of psychotropic agents on stroke risk among patients with bipolar disorders. RESULTS: The results indicated that overall use of psychotropic agents was associated with an increased risk of stroke (adjusted odds ratio [AOR] = 1.82; 95% confidence interval [CI]: 1.56-2.13). When classifying psychotropic agents into antipsychotics, antidepressants and mood stabilizers, respectively, a significant positive association was found for users of antipsychotics (AOR = 1.98; 95% CI = 1.53-2.56), antidepressants (AOR = 1.44; 95% CI = 1.16-1.79), and mood stabilizers (AOR = 1.89; 95% CI = 1.22-2.93). Combined use of psychotropic agents was associated with higher risk of stroke than monotherapy (AOR = 2.62; 95% CI = 1.98-3.45). DISCUSSIONS: The results support our hypothesis that psychotropic use is associated with increased risk of stroke among patients with bipolar disorders. The stroke risks are higher among patients with polypharmacy than those with monotherapy. These findings warrant further investigation to confirm and replicate the findings using different methodologies and populations, and to mitigate residual confounding.

Suicide deaths among patients with end-stage renal disease receiving dialysis: A population-based retrospective cohort study of 64,000 patients in Taiwan.

BACKGROUND: Patients with end-stage renal disease (ESRD) who receive dialysis may experience increased distress and risk of suicide. METHODS: This population-based retrospective cohort study linked Taiwan's national register of ESRD patients on dialysis and the cause-of-death mortality data file. A separate multiple-cause-of-death data file was used to investigate the detailed suicide methods used. Standardized mortality ratios (SMRs) were calculated for the overall patient group and by sex, age, year of initiating dialysis, method of suicide, and time since initiation of dialysis. RESULTS: Among 63,854 ESRD patients on dialysis, 133 died by suicide in Taiwan in 2006-2012; the suicide rate was 76.3 per 100,000 patient-years. The SMR for suicide was 2.38 (95% confidence interval [CI] 1.99-2.82) in this patient group. Suicide risk was highest in the first year of dialysis (SMR = 3.15, 95% CI 2.39-4.08). The risk of suicide by cutting was nearly 20 times (SMR = 19.91, 95% CI 12.88-29.39) that of the general population. Detailed information on death certificates indicated that three quarters of patients who killed themselves by cutting cut vascular accesses used for hemodialysis. LIMITATIONS: Information on risk factors such as socioeconomic position and mental disorders was unavailable. CONCLUSION: In a country where the national health insurance program covers most expenses associated with dialysis treatment, the suicide risk in ESRD patients on dialysis still increased nearly 140%. Adequate support for ESRD patients initiating dialysis and the assessment of risk of cutting vascular access as a potential means of suicide could be important strategies for suicide prevention.

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.

Comparative Risk of Ventricular Arrhythmia and Sudden Cardiac Death Across Antidepressants in Patients With Depressive Disorders.

OBJECTIVE: We aimed to evaluate the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with antidepressant use. METHODS: A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 793,460 new antidepressant users with depressive disorders were enrolled in the study. Outcomes were defined as the first principal diagnosis of VA or SCD in the emergency department or hospital discharge records. Cox proportional hazards models with stratification of propensity score deciles were used to evaluate the relative risk of VA/SCD for antidepressants compared with selective serotonin reuptake inhibitors (SSRIs). RESULTS: A total of 245 VA/SCD events occurred. The incidence rate of VA/SCD among antidepressant users was 1.5 per 1000 person-years (95% confidence interval [CI], 1.3-1.7). Compared with SSRIs, the risk of VA/SCD was significantly lower for tricyclic or tetracyclic antidepressant (TCAs) (adjusted hazards ratio [aHR], 0.54; 95% CI, 0.36-0.83), but not other antidepressant classes. However, use of moderate- to high-dose TCAs carried a higher risk than low-dose TCAs (aHR, 4.37; 95% CI, 1.23-15.60). Antidepressant polypharmacy was associated with an increased risk of VA/SCD (aHR, 1.63; 95% CI, 1.07-2.49). CONCLUSIONS: There was no difference in VA/SCD risk across antidepressant classes except that TCAs were associated with a lower risk than SSRIs. However, the observed comparative risk of TCAs might be attributable to low-dose TCA use, which is quite common in current clinical practice. It would be of importance to carry out further investigations to scrutinize the influence of antidepressants on VA/SCD.

Comparison of treatment effectiveness and medical costs for different long-acting injectable antipsychotics in patients with schizophrenia in Taiwan: A nationwide population-based cohort study.

OBJECTIVE: To assess the comparative effectiveness and medical costs of five long-acting injectable (LAI) antipsychotics, flupentixol, fluphenazine, haloperidol, risperidone, and clopentixol/zuclopentixol, in patients with schizophrenia. METHOD: We conducted a retrospective cohort study of patients with schizophrenia using data from Taiwan's National Health Insurance Research Database. Patients aged 15years or older who began treatment with LAI antipsychotics between June 1, 2004 and December 31, 2008 were enrolled and followed for 1year. We evaluated the medical costs and treatment effectiveness, which was assessed using the rates of treatment discontinuation, psychiatric hospitalization, and emergency department visits. Risperidone was used as a reference group. RESULTS: Compared to risperidone, flupentixol was associated with higher hazard ratios of treatment discontinuation and psychiatric hospitalization, fluphenazine was associated with higher hazard ratios of treatment discontinuation, and haloperidol was associated with higher rates of psychiatric hospitalization and emergence department visits. However, fluphenazine, flupentixol, and haloperidol were associated with lower medical costs compared to risperidone. Clopentixol/zuclopentixol was inferior to risperidone in treatment effectiveness and medical cost. CONCLUSIONS: Our findings suggest that patients taking the LAI risperidone may be more effective in some but not all outcome measures; however, risperidone was also associated with higher medical costs in the Taiwanese healthcare setting.

Antipsychotic drugs and the risk of ventricular arrhythmia and/or sudden cardiac death: a nation-wide case-crossover study.

BACKGROUND: Antipsychotics have been linked to prolongation of the QT interval. However, little is known about the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with individual antipsychotic drug use. This study was designed to investigate the association between specific antipsychotic drugs and the risk of VA and/or SCD. METHODS AND RESULTS: We conducted a case-crossover study using a nation-wide population-based sample obtained from Taiwan's National Health Insurance Research Database. A total of 17 718 patients with incident VA and/or SCD were enrolled. Conditional logistic regression models were applied to examine the effects of antipsychotic drug use on the risk of VA/SCD during various case and control time windows of 7, 14, and 28 days. The effect of the potency of a human ether-à-go-go-related gene (hERG) potassium channel blockade was also assessed. Antipsychotic drug use was associated with a 1.53-fold increased risk of VA and/or SCD. Antipsychotic drugs with increased risk included clothiapine, haloperidol, prochlorperazine, thioridazine, olanzapine, quetiapine, risperidone, and sulpiride. The association was significantly higher among those with short-term use. Antipsychotics with a high potency of the hERG potassium channel blockade had the highest risk of VA and/or SCD. CONCLUSION: Use of antipsychotic drugs is associated with an increased risk of VA and/or SCD. Careful evaluations of the risks and benefits of antipsychotic treatment are highly recommended.

Ovarian cancer and antidepressants.

BACKGROUND: The association between antidepressant use and ovarian cancer remains unclear. This study aimed to assess the ovarian cancer risk with antidepressant use in the general population. METHODS: Taiwan's National Health Insurance Research Database was used to identify 957 patients with ovarian cancer and 9570 controls. We used a conditional logistic regression model for data analysis, excluding a 1-year latent period before the diagnosis of ovarian cancer to account for the quantification of treatment duration. RESULTS: We found no increased risk of developing ovarian cancer among antidepressant users. Neither the duration of antidepressant use nor the average dose had a significant effect on the risk of ovarian cancer. In addition, timing of antidepressant use was not linked to ovarian cancer risk. However, we found the estimate of ovarian cancer risk increased slightly among subjects under 50 years (adjusted OR = 2.03, 95% CI [0.82, 5.02]), although this association was still statistically insignificant (p = 0.12). CONCLUSIONS: There was no association between risk of ovarian cancer and use of antidepressant drugs. Whether or not there is possible risk of using antidepressant whose mechanism of action involves dopamine and norepinephrine warrants further investigation.

Concordance between patient self-reports and claims data on clinical diagnoses, medication use, and health system utilization in Taiwan.

PURPOSE: The aim of this study was to evaluate the concordance between claims records in the National Health Insurance Research Database and patient self-reports on clinical diagnoses, medication use, and health system utilization. METHODS: In this study, we used the data of 15,574 participants collected from the 2005 Taiwan National Health Interview Survey. We assessed positive agreement, negative agreement, and Cohen's kappa statistics to examine the concordance between claims records and patient self-reports. RESULTS: Kappa values were 0.43, 0.64, and 0.61 for clinical diagnoses, medication use, and health system utilization, respectively. Using a strict algorithm to identify the clinical diagnoses recorded in claims records could improve the negative agreement; however, the effect on positive agreement and kappa was diverse across various conditions. CONCLUSION: We found that the overall concordance between claims records in the National Health Insurance Research Database and patient self-reports in the Taiwan National Health Interview Survey was moderate for clinical diagnosis and substantial for both medication use and health system utilization.

Long-term statin use and dementia risk in Taiwan.

BACKGROUND: The effect of statin use on dementia risk remains unclear. This study aims to examine the association between long-term statin use and dementia risk. METHODS: A nest case-control study within a nationwide representative population-based cohort. Individuals aged 50 years and older participating in Taiwan's National Health Insurance program between 1998 and 2009 were enrolled. A total of 9257 patients with at least 3 outpatient or 1 inpatient claims records for dementia were identified. Comparison patients were selected at a 1:2 ratio from age- and sex-matched participants without dementia. The cumulative period and average daily dosages of statins, fibrates, and other lipid-lowering agents were measured. RESULTS: The authors found a duration-response relationship, as dementia risk decreased by 9% per year of treatment of statins (adjusted odds ratio = 0.91; 95% confidence interval, 0.85-0.97). Use of high average dose statins for more than 1 year was associated with a lower risk of dementia than use of low average dose. However, there was no significant difference in dementia risks between lipophilic and hydrophilic statins. Fibrates or other lipid-lowering agents had no significant association with dementia risk. CONCLUSION: Our results suggest that long-term use of statin is associated with a reduced dementia risk.

Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.

Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.

Increased risk of developing dementia in patients with bipolar disorder: a nested matched case-control study.

OBJECTIVE: The association between bipolar disorder and subsequent dementia risk is not well established. The objective of this study was to investigate whether patients with bipolar disorder were at an increased risk for developing dementia. METHODS: A conditional logistic regression model was performed using data from the National Health Insurance Research Database, a nationwide dataset in Taiwan. The study sample included 9,304 patients with incident dementia first diagnosed between 2000 and 2009, and 55,500 gender-, age-, and index date-matched subjects without dementia. Cerebrovascular disease, diabetes, hypertension, head injury, chronic pulmonary disease, alcohol-related disorders, substance use disorders, and health system utilization were treated as covariates in the analyses. RESULTS: After controlling for the covariates, bipolar disorder was significantly associated with an increased risk of subsequent dementia [adjusted odds ratio (aOR) = 4.32, 95% confidence interval (CI): 3.21-5.82]. An increased risk of developing dementia was observed in males and females alike (aOR = 4.01, 95% CI: 2.53-6.35 in males; aOR = 4.55, 95% CI: 3.07-6.73 in females). Moreover, a significantly increased risk was observed in subjects diagnosed with dementia before the age of 65 years (aOR = 3.77, 95% CI: 1.78-8.01). CONCLUSIONS: Findings from this study suggest a positive association between the presence of a lifetime history of bipolar disorder and an increased risk of developing dementia. Furthermore, our results also suggest that subjects with bipolar disorder tend to develop dementia in middle age. Going forward, it will be of importance to confirm our findings in different populations.

UGT2B7 genetic polymorphisms are associated with the withdrawal symptoms in methadone maintenance patients.

AIM: To test whether the genetic polymorphisms within the gene encoding the UGT2B7 gene may have an impact on methadone treatment. MATERIALS & METHODS: Twelve SNPs in UGT2B7 were selected. 366 methadone maintenance treatment patients in Taiwan were recruited and genotyped. RESULTS: In a genotype recessive model, rs6600879, rs6600880, rs4554144, rs11940316, rs7438135, rs7662029, rs7668258, rs7439366, rs4292394 and rs6600893 showed significant associations with severity of withdrawal symptoms (permutation p < 0.002), pupil size (permutation p < 0.048) and tremor (permutation p < 0.008). Haplotypes of GATCAGCCGC and CTCTGATTCT were significantly associated with pupil size score and tremor score (p < 0.034). CONCLUSION: These results suggest that SNPs of the UGT2B7 gene may play important roles in opiate withdrawal symptoms.