Protective Effect of Escitalopram on Hepatocellular Carcinoma by Inducing Autophagy.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with poor prognosis. Although recent research has indicated that selective serotonin reuptake inhibitors (SSRIs), including escitalopram, have anticancer effects, little is known about the effects of escitalopram on HCC. METHODS: Both in vitro and in vivo studies were conducted to verify the potentials of escitalopram on HCC treatment. To explore whether the effects of escitalopram are clinically consistent with laboratory findings, a nationwide population-based cohort study was also adopted to examine the association between escitalopram and HCC risk. RESULTS: As compared with THLE-3 cells, escitalopram significantly inhibited the proliferation of HepG2 and Huh-7 cells. Specifically, escitalopram significantly induced autophagy in HepG2 and Huh-7 cells by increasing the LC3-II/LC3-I ratio and the expression of ATG-3, ATG-5, ATG-7, and Beclin-1 proteins. Moreover, escitalopram significantly inhibited the growth of xenografted Huh-7 cells in SCID mice that were treated with 12.5 mg/kg escitalopram. Accordingly, the risk of HCC was negatively correlated with escitalopram use. CONCLUSIONS: These findings provided evidence supporting the therapeutic potential of escitalopram for HCC. Both laboratory and nationwide population-based cohort evidence demonstrated the attenuated effects of escitalopram on HCC.

Association of Risperidone With Gastric Cancer: Triangulation Method From Cell Study, Animal Study, and Cohort Study.

Purpose: To examine the effects of risperidone, an atypical antipsychotic agent, on gastric cancer. Methods: A triangulation method comprising bench studies, including cell and animal experiments, and a retrospective cohort study, was subsequently performed. Results: The bench study indicated that risperidone exerted more prominent tumor inhibition effects than other atypical antipsychotics on the proliferation of KATO-III cells, a human gastric cancer cell line. Significant and dose-dependent cell viability was observed in Hs27 cells (control cells) in the presence of risperidone compared with in KATO-III cells. Both in vivo and in vitro results indicated that risperidone significantly inhibited the proliferation of KATO-III cells by inducing ROS and apoptosis, and that it suppressed the growth of xenografted KATO-III tumors in nude mice. In addition, the population-based cohort study found that risperidone users had reduced risks of gastric cancer compared with non-users, with lowered adjusted hazard ratios (HRs) for two induction periods (HR = 0.75; 95% confidence interval [CI] 0.68-0.83 for the one-year induction period, and HR = 0.68; 95% CI 0.61-0.75 for the two-year induction period). Conclusion: The findings are consistent with anticancer effects associated with risperidone, but further research and evaluations are warranted.

Urine metabolic phenotyping in children with nocturnal enuresis and comorbid neurobehavioral disorders.

Nocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Nevertheless, increasing evidence suggests a potential link between neurobehavioral disorders and enuresis in children. In this study, we aimed to explore novel metabolomic insights into the pathophysiology of NE and also, its association with pediatric psychiatric problems. Urine collected from 41 bedwetting children and 27 healthy control children was analyzed by using 1H-nuclear magnetic resonance spectroscopy from August 2017 to December 2018. At regular follow-up, there were 14 children with refractory NE having a diagnosis of attention deficient hyperactivity disorder (ADHD) or anxiety. Eventually, we identified eight significantly differential urinary metabolites and particularly increased urinary excretion of betaine, creatine and guanidinoacetate linked to glycine, serine and threonine metabolism were associated with a comorbidity of neurobehavioral disorders in refractory bedwetting children. Notably, based on physiological functions of betaine acting as a renal osmolyte and methyl group donor, we speculated its potential role in modulation of renal and/or central circadian clock systems, becoming a useful urinary metabolic marker in diagnosis of treatment-resistant NE in children affected by these two disorders.

Antipsychotic use is inversely associated with gastric cancer risk: A nationwide population-based nested case-control study.

OBJECTIVE: The association between antipsychotic use and gastric cancer risk remains unclear. Therefore, this study aimed to determine the association between antipsychotic exposure and the incidence of gastric cancer. METHODS: Using a nested case-control design, a total of 34 470 gastric cancer patients and 163 430 nongastric cancer controls were identified from Taiwan's National Health Insurance Research Database between 1 January 1997 and 31 December 2013. We analyzed the data using a conditional logistic regression model to adjust for possible confounding variables. RESULTS: Antipsychotic use was independently inversely associated with gastric cancer risk after controlling for potential confounding factors including income, urbanization, medications, physical and medical illness, aspirin use, nonsteroidal anti-inflammatory drug use and triple therapy. In addition, dose-dependent trends against gastric cancer risk were also shown with individual antipsychotic compounds including thioridazine, haloperidol, sulpiride, clozapine, olanzapine, quetiapine, amisulpride, and risperidone. A sensitivity analysis showed that second-generation antipsychotics had significant dose-dependent effects in reducing the risk of gastric cancer risk in patients with and without peptic ulcer disease. CONCLUSIONS: Antipsychotic use was inversely associated with gastric cancer risk, and dose-dependent effects against gastric cancer were also seen with several individual antipsychotic compounds.

Antidepressant medication use and nasopharyngeal cancer risk: a nationwide population-based study.

BACKGROUND: The association between antidepressant exposure and nasopharyngeal cancer (NPC) has not been previously explored. The purpose of this study was to investigate the association between antidepressant prescription, including novel antidepressants, and the risk of NPC in a population-based study. MATERIALS AND METHODS: Data for the analysis were derived from National Health Insurance Research Database. We identified 16,957 cases with a diagnosis of NPC and 83,231 matched controls by using a nested case-control design. A conditional logistic regression model was used, with adjustments for potentially confounding variables (eg, comorbid physical diseases, comorbid psychiatric diseases, and other medications). RESULTS: We report no association between NPC incidence and antidepressant prescription. For all classes of antidepressants, antidepressant exposure, regardless of cumulative dose, had no significant effect on NPC incidence (adjusted odds ratio of cumulative selective serotonin reuptake inhibitor exposure ≥336 defined daily dose was 1.18 [95% CI: 0.90-1.53]; tricyclic antidepressant exposure ≥336 defined daily dose was 1.18 [95% CI: 0.80-1.74]). CONCLUSION: There was no association between antidepressant prescription and incident NPC.

Hepatocellular carcinoma and antidepressants: a nationwide population-based study.

Hepatocellular carcinoma (HCC) is highly prevalent in Asia. Antidepressants have been associated with increase in hepatocellular carcinoma. This is the first Asian population-based study to evaluate the association between antidepressant use and risk of HCC. Based on Taiwan's National Health Insurance Research Database, we conducted a nationwide population-based study. A total of 49,998 cases with HCC were identified and paired with 244,236 randomly selected controls. The data was analyzed via the conditional logistic regression model adjusting for several confounding factors. Use of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) was associated with lower risk for HCC. No apparent association was found between use of other classes of antidepressants and HCC, including monoamine oxidase inhibitors (MAOIs), serotonin norepinephrine reuptake inhibitors (SNRIs), trazodone, mirtazapine and bupropion. The findings of a protective effect of TCAs and SSRIs for HCC should be interpreted with caution and warrants further research.

Endometrial cancer and antidepressants: A nationwide population-based study.

To our knowledge, the association between antidepressant exposure and endometrial cancer has not been previously explored. Herein, we aim to investigate the association between antidepressant prescription, including novel antidepressants, and the risk for endometrial cancer in a population-based study.Data for the analysis were derived from National Health Insurance Research Database. We identified 8392 cases with a diagnosis of endometrial cancer and 82,432 matched controls. A conditional logistic regression model was used, with adjusting for potentially confounding variables (e.g., comorbid psychiatric diseases, comorbid physical diseases, and other medications). Risk for endometrial cancer in the population-based study sample was categorized by, and assessed as a function of, antidepressant prescription and cumulative dosage.We report no association between endometrial cancer incidence and antidepressant prescription, including those prescribed either selective serotonin reuptake inhibitors (adjusted odds ratio [OR] = 0.98; 95% confidence interval [CI], 0.84-1.15) or serotonin norepinephrine reuptake inhibitors (adjusted OR = 1.14; 95% CI, 0.76-1.71). We also did not identify an association between higher cumulative doses of antidepressant prescription and endometrial cancer.There was no association between antidepressant prescription and endometrial cancer.

Antidepressants and Gastric Cancer: A Nationwide Population-Based Nested Case-Control Study.

BACKGROUND: To our knowledge, no epidemiological study has reported on whether an association between antidepressant exposure and gastric cancer exists. Herein, we aim to investigate the possible association between antidepressant exposure and gastric cancer incidence. METHODS: Using a nested case-control design, we identified 26289 cases with gastric cancer and 127984 controls from Taiwan's National Health Insurance Research Database (NHIRD). The data were analyzed using a conditional logistic regression model adjusting for possible confounding variables. RESULTS: We found antidepressant use did not increase the risk of gastric cancer. The lack of an association between antidepressant prescription and elevated gastric cancer incidence was apparent for across selective serotonin-reuptake inhibitors (SSRIs), tricyclic agents (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), reversible inhibitors of monoamine oxidase A (RIMA), trazodone, mirtazapine and bupropion. There were slightly decreased gastric cancer risks of SSRIs use (≧28 DDD group, adjusted OR = 0.87; 95% CI = 0.78-0.96). Sensitive analysis showed SSRIs, TCAs, and SNRIs did not increase gastric cancer risks significantly even in the group with peptic ulcer history. CONCLUSIONS: An association between antidepressant exposure and gastric cancer was not apparent in this analysis.

Invasive Cervical Cancer and Antidepressants: A Nationwide Population-Based Study.

To our knowledge, no prior population-based study has been published wherein the primary aim was to evaluate whether an association between psychotropic drug prescription and cervical cancer exists. Herein we have conducted the first study that primarily aimed to determine the association between antidepressants use and risk of invasive cervical cancer in the general population.This is a population-based study utilizing Taiwan's National Health Insurance Research Database. We identified 26,262 cases with invasive cervical cancer and 129,490 controls. We adopted the conditional logistic regression model as the statistical method and adjusted for potential confounding factors.The prescription of selective serotonin reuptake inhibitors (SSRIs) (adjusted OR = 0.93, 95% CI = 0.84-1.04), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin norepinephrine reuptake inhibitors (SNRIs), mirtazapine and bupropion, adjusting for cumulative dose, was not associated with an increased, or decreased, risk for invasive cervical cancer. An association between trazodone prescription and invasive cervical cancer was observed (adjusted OR = 1.22, 95% CI = 1.03-1.43).An association between the major classes of antidepressants and invasive cervical cancer was not observed herein. Our preliminary finding regarding a possible association between trazodone and cervical cancer requires replication.