Psychotropic medications and mortality from cardiovascular disease and suicide for individuals with depression in Taiwan.

BACKGROUND: Polypharmacy for treatment of depression has been increasing in Taiwan. METHODS: Individuals having depressive disorders were identified in a national database for healthcare services and followed up for 5 years. The mean dosage of antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics was calculated; the associations between the exposure dosage to different psychotropic medications and patients' overall death and death due to cardiovascular diseases (CVD) and suicide were examined. RESULTS: A total of 400,042 individuals with depressive disorders (63.8% women) were identified. Compared with those with no exposure to antidepressants, patients prescribed antidepressants had decreased mortality. Use of antipsychotics had a dose-related increase in overall mortality risk compared to no exposure group. Contrarily, depressed patients taking sedative-hypnotics had decreased overall and CVD mortality compared to no exposure group, with the most prominent decrease in CVD mortality of up to 54.9% for those in the moderate exposure group (hazard ratio: 0.451, 95% confidence interval: 0.405-0.503). A moderate or high dose of antidepressants or sedative-hypnotics was shown to be associated with a significantly increased mortality for suicide compared to those with no exposure. CONCLUSIONS: Antidepressant and sedative-hypnotic use was associated with decreased all-cause and CVD-related mortality and use of antipsychotics was associated with a dose-related increase in mortality risk. Future studies are needed to further clarify the involved mechanisms and benefits and risks should be carefully weighed when prescribing psychotropic medications in patients with depressive disorders.

Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study.

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS.

Ultrasound reduces inflammation by modulating M1/M2 polarization of microglia through STAT1/STAT6/PPARγ signaling pathways.

INTRODUCTION: Activated microglia can be polarized to the pro-inflammatory M1 phenotype and the anti-inflammatory M2 phenotype. Low-intensity pulsed ultrasound (LIPUS) can attenuate pro-inflammatory responses in activated microglia. OBJECTIVE: This study aimed to investigate the effects of LIPUS on M1/M2 polarization of microglial cells and the regulatory mechanisms associated with signaling pathways. METHODS: BV-2 microglial cells were stimulated by lipopolysaccharide (LPS) to an M1 phenotype or by interleukin-4 (IL-4) to an M2 phenotype. Some microglial cells were exposed to LIPUS, while others were not. M1/M2 marker mRNA and protein expression were measured using real-time polymerase chain reaction and western blot, respectively. Immunofluorescence staining was performed to determine inducible nitric oxide synthase (iNOS)-/arginase-1 (Arg-1)- and CD68-/CD206-positive cells. RESULTS: LIPUS treatment significantly attenuated LPS-induced increases in inflammatory markers (iNOS, tumor necrosis factor-α, interleukin-1ß, and interleukin-6) as well as the expression of cell surface markers (CD86 and CD68) of M1-polarized microglia. In contrast, LIPUS treatment significantly enhanced the expression of M2-related markers (Arg-1, IL-10, and Ym1) and membrane protein (CD206). LIPUS treatment prevented M1 polarization of microglia and enhanced or sustained M2 polarization by regulating M1/M2 polarization through the signal transducer and activator of transcription 1/STAT6/peroxisome proliferator-activated receptor gamma pathways. CONCLUSIONS: Our findings suggest that LIPUS inhibits microglial polarization and switches microglia from the M1 to the M2 phenotype.

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.

Quetiapine ameliorates collagen-induced arthritis in mice via the suppression of the AKT and ERK signaling pathways.

OBJECTIVE AND DESIGN: To investigate the amelioration effects of quetiapine on rheumatoid arthritis with RAW 264.7 macrophage and collagen-induced arthritis (CIA) DBA/1J mouse model. SUBJECTS: RAW 264.7 macrophage and DBA/1J mice. TREATMENT: Lipopolysaccharide and collagen. METHODS: RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) followed by quetiapine treatments were investigated. Activations of CD80 and CD86 were analyzed by flow cytometry. Pro-inflammatory cytokines such as IL-6, TNF-α and IL-1ß were analyzed by ELISA. Proteins involved in signaling pathways related to the formation of rheumatoid arthritis were assayed by Western blotting. Therapeutic efficacy of quetiapine in CIA mouse model was also assayed. 18F-FDG/micro-PET was used to monitor the inflammation status in the joints, and the severity of bone erosion was evaluated with micro-CT and H&E staining. RESULTS: The inhibition of pro-inflammatory cytokines by quetiapine was found through the ERK and AKT phosphorylation and subsequent NF-κB and CREB signaling pathways. Pro-inflammatory cytokines such as IL-17, IL-6 and IL-1ß were decreased, while immunosuppressive factors such as TGF-ß and IL-10 were increased in CIA mice treated with quetiapine. Notably, no uptake of 18F-FDG and bone erosion was found with micro-PET images on days 32 and 43 in the quetiapine-treated and normal control groups. However, significant uptake of 18F-FDG could be observed in the CIA group during the same time course. Similar results were further verified with ex vivo autoradiography. CONCLUSION: Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.

Three-year mortality in relation to early hospitalization and number of outpatient clinic visits in people with newly diagnosed bipolar disorder.

OBJECTIVE: Whether the early treatment pattern in people with bipolar disorder (BD) could influence later mortality remains to be determined. We aimed to explore the potential effects of early hospitalization and number of outpatient clinic visits on the 3-year mortality in patients with newly diagnosed BD. METHOD: Adult participants with newly diagnosed BD were identified in Taiwan's National Health Insurance Research Database in 2008. Survival analyses were performed with this national cohort to examine the associations between the first-year treatment pattern (hospitalization and number of outpatient clinic visits) and mortality over a follow-up period of 3 years (2008-2011). RESULTS: A total of 15,254 participants were included. The mean age was 44.9 (S.D.=16.7) years and around 39.9% were male. The average follow-up time was 1055 days. Compared to BD patients with ≥7 times outpatient clinic visits within the first year, the risk of mortality was found elevated [hazard ratio=1.74; 95% confidence interval (CI), 1.40-2.15] for those who needed inpatient treatment. Number of outpatient clinic visits within the first year was found to be negatively associated with later mortality. Besides cancer (hazard ratio=2.14; 95% CI, 1.74-2.63), diabetes mellitus (hazard ratio=1.61; 95% CI, 1.38-1.89) and renal disease (hazard ratio=1.65; 95% CI, 1.36-2.00) were associated with the highest risk of mortality among the physical comorbidities. Substance use disorder stood out as the single comorbid mental illness associated with the highest mortality risk (hazard ratio=1.74; 95% CI, 1.37-2.21). CONCLUSIONS: Early treatment pattern, including hospitalization and number of outpatient clinic visits, was associated with later mortality in BD patients. Special care should be given to enhance treatment adherence and to give psychoeducation to those with certain comorbid mental/physical illnesses to reduce health harming behavior and to improve health outcome.

Carotid blowout and cerebral gas embolism related to bidirectional carotid-esophageal fistula: a serious complication of esophageal cancer under radiotherapy.

Carotid-esophageal fistula (CEF) could be a serious complication of esophageal cancer in a patient receiving radiotherapy. We reported a 47-year-old male patient with advanced cervical esophageal cancer under radiotherapy who developed CEF with the presentations of unstable vital signs and disturbances of consciousness. Carotid-esophageal fistula-associated life-threatening conditions of carotid blowout syndrome and cerebral gas embolism were diagnosed after presentation. Subsequently, intramural dissection of esophageal and gastric walls, profound hemoperitoneum, and hypovolemic shock occurred. When a patient who had an underlying cervical esophageal cancer treated by radiotherapy develops unstable vital signs and neurological symptoms, CEF should be kept in mind in the differential diagnoses. Physicians must be alert of the associated complications of carotid blowout syndrome and cerebral gas embolism and perform timely management including decompression, fluid resuscitation, and aggressive endovascular procedure when indicated.

Depression and pain: an appraisal of cost effectiveness and cost utility of antidepressants.

BACKGROUND: Although depression and chronic pain frequently co-occur, there is a lack of clarity in the literature regarding the cost-effectiveness and cost-utility of antidepressants in the presence of these two conditions. From the perspective of healthcare provider, the current study aims to compare the cost-effectiveness and cost-utility of antidepressants in a national cohort of depressed patients with and without comorbid pain conditions. METHODS: Adult patients prescribed with antidepressants for depression were identified from the National Health Insurance Research Database in Taiwan (n=96,501). By using remission as effectiveness measure and quality-adjusted life years (QALYs) as utility measure, the cost-effectiveness and cost-utility were compared across selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs), as well as by the presence of comorbid painful physical symptoms (PPS). RESULTS: SSRIs dominated SNRIs in both the cost-effectiveness and cost-utility regardless of comorbid PPS. In comparison with TCAs, SSRIs were likely to be the cost-effective option for patients without PPS. In patients with PPS, the cost-utility advantage for SSRIs over TCAs varied with threshold willingness-to-pay levels. Comorbid PPS may be considered an effect modifier of the cost-utility comparisons between SSRIs and TCAs. CONCLUSIONS: For depressed patients without PPS, SSRIs are likely to be cost-effective in improving remission rates and QALYs compared to TCAs and SNRIs. However, to improve cost-utility in those with comorbid PPS, people need to choose between SSRIs and TCAs according to threshold willingness-to-pay levels. Future research is warranted to clarify the impacts of different pain conditions on the economic evaluations of pharmacological treatments in patients with depression.

Cost-effectiveness and cost-utility of selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants in depression with comorbid cardiovascular disease.

OBJECTIVE: There is a lack of clarity in the literature regarding the cost-effectiveness and cost-utility of antidepressants for treating real-world patients. The impact of comorbid cardiovascular disease (CVD) on the economic evaluations of antidepressants remains to be determined. METHOD: Adult patients prescribed with antidepressants for depression were identified from the National Health Insurance Research Database in Taiwan. A cost-effectiveness and cost-utility analysis was conducted comparing selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs), and by the presence of comorbid CVD. RESULTS: In terms of treatment success rates, SSRIs were the most cost-effective option compared to TCAs and SNRIs as revealed in the incremental cost-effectiveness ratios. The cost-effectiveness acceptability curves further showed differential findings in the cost-utility results by the presence of comorbid CVD. CONCLUSION: To improve treatment success rates and quality-adjusted life years, SSRIs can be considered the most cost-effective option. Future research is needed to further clarify the impacts of physical comorbidities and other associated factors on the cost-effectiveness and cost-utility of pharmacological treatments in patients with depression.

Physician suicide in Taiwan, 2000-2008: preliminary findings.

Research regarding physician suicide in Taiwan is lacking. Using national physician insurance data from January 1, 2000 to April 30, 2008, the present study aimed to explore the association between physicians' suicide and their characteristics, including age, sex, specialties, area of residence, hospital types, and suicide methods. The majority (53.1-70.6%) of suicide cases occurred among physicians in their 40s. More suicides were reported among physicians serving in the community, living in urban areas, and from specialties such as general practice, family practice, psychiatry, and surgery. The leading suicide methods were hanging/suffocation, drowning, jumping from heights, charcoal burning and drug poisoning. In conclusion, physicians committing suicide were likely to be in their 40s, to serve in the community and to live in urban areas. Future efforts should focus on exploring the causes and possible interventions for physician suicide.