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Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

Cheng-Chen Chang, 1, 2,* Wen-Fu Wang, 3, 4,* Yi-Ying Li, 5,* Yu-An Chen, 1 Yen-Jen Chen, 1 Yi-Cheng Liao, 1 Kai-Ming Jhang, 3 Hsin-Hung Wu 5– 7 1Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung City, Taiwan; 3Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan; 4Department of Holistic Wellness, Ming Dao University, Changhua, Taiwan; 5Department of Business Administration, National Changhua University of Education, Changhua, Taiwan; 6Department of M-Commerce and Multimedia Applications, Asia University, Taichung City, Taiwan; 7Faculty of Education, State University of Malang, Malang, East Java, Indonesia*These authors contributed equally to this workCorrespondence: Hsin-Hung Wu Email hhwu@cc.ncue.edu.twPurpose: The purpose of this study was to identify the caring scenarios that result in severe depression in caregivers caring for dementia patients.Patients and Methods: A cross-sectional study with 1111 dementia patients and their caregivers in Taiwan from October 2015 to January 2020 was conducted. Gender, age, type of dementia, clinical dementia rating, walking ability, mood symptoms, behavioral symptoms, and psychological symptoms were the variables from the dementia patients. Age, relation to the patient, employment, type of primary care, frequency of care, mood symptoms, and the score from the Center for Epidemiologic Studies Depression Scale were the variables from the caregivers. A comprehensive viewpoint of both dementia patients and their caregivers was evaluated by the Apriori algorithm to find the attributes resulting in different caregiving depressions.Results: Forty-seven rules were found with 18 rules of mild depressive symptomatology, 17 rules of moderate depressive symptomatology, and 12 rules of severe depressive symptomatology. A total of 7 general rules were summarized to be the severe depressive symptomatology. The results showed that an unemployed or retired caregiver with the mood symptoms such as helplessness, anger, emotional liability, or anxiety who took care of AD patients or AD patients with a moderate severity would have severe depression. Increased care frequencies (≥ 6 days per week) and multiple mood problems from caregivers result in severe depression. The composition of adult children, patients’ aggression, and caregivers’ helplessness as well as the combinations of male patients aged 75– 84 years with the caregiver’s mood of helplessness or nervousness and hopelessness were highly associated with severe depression.Conclusion: For those caring for AD patients, severe depression was associated with the combination of different parameters to constitute each of these seven scenarios. Unlike previous studies which often evaluated one or two variables related to caregiver’s depression, this study provided a more comprehensive viewpoint that enabled the collaborative team to efficiently identify and manage different scenarios by summarizing the rules of caregivers with severe depression from a systematic viewpoint.Keywords: patient with dementia, Alzheimer’s disease, behavioral and psychological symptoms of dementia, caregiver, caregiver’s mood, depressive symptomatology, Center for Epidemiologic Studies Depression Scale, caring scenario, Apriori algorithm

Yu-An Chen,1,* Cheng-Chen Chang,1,2,* Wen-Fu Wang,3,4,* Ya-Sian Lin,5 Kai-Ming Jhang,3 Tzu-Ying Lo,5 Hsin-Hung Wu5– 7 1Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung City, Taiwan; 3Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan; 4Department of Holistic Wellness, Ming Dao University, Changhua, Taiwan; 5Department of Business Administration, National Changhua University of Education, Changhua, Taiwan; 6Department of M-Commerce and Multimedia Applications, Asia University, Taichung City, Taiwan; 7Faculty of Education, State University of Malang, Malang, East Java, Indonesia*These authors contributed equally to this workCorrespondence: Hsin-Hung WuNational Changhua University of Education, No. 2 Shida Road, Changhua City, 500, TaiwanTel +886 4 7232105 ext. 7412Fax +886 4-7211292Email hhwu@cc.ncue.edu.twPurpose: This study examined the attributes causing higher burdens for caregivers caring for female patients with Alzheimer’s disease by analyzing a combination of various variables, including demographic data, dementia severity, and neuropsychiatric symptoms.Patients and Methods: This study included 99 female patients with Alzheimer’s disease who were cared for by the dementia collaborative care team at Changhua Christian Hospital, Taiwan. Neuropsychiatric symptoms used in this study included affections (9 types), behavior symptoms (9 symptoms), and psychological symptoms (3 symptoms). The Apriori algorithm was employed to identify association rules that reveal the relationships among demographic data, dementia severity, neuropsychiatric symptoms, and caregivers’ burden.Results: A total of 185 rules were determined, including 51 rules with little or no burden, 108 rules with mild to moderate burden, and 26 rules with moderate to severe burden. The major findings are as follows. Neuropsychiatric symptoms were associated with varying degrees of caregivers’ burden among female patients aged 75 to 84 years with mild dementia. Crying spells and aggression were specifically associated with a moderate to severe burden. Delusion was associated with a mild to moderate and moderate to severe burden. Dysthymia and depression were associated with little or no burden to moderate to severe burden.Conclusion: Clinicians can provide early interventions to reduce the burden of caregivers caring for female patients with Alzheimer’s disease and can refer caregivers for timely assistance to reduce their burden.Keywords: Alzheimer’s disease, female patients, female patients with Alzheimer’s disease, neuropsychiatric symptom, Apriori algorithm, caregiving burden

Background: Using data from the National Health Insurance (NHI) of Taiwan, we conducted a nationwide population-based cohort study to investigate the association between antidepressant (ATD) use and the risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) who had received interferon (IFN) therapy. Methods: This study included a total of 274,952 HCV-infected patients without hepatitis B virus infection who were enrolled in the NHI program between January 1, 1997 and December 31, 2013. Among these patients, only 10,713 (age ≥18 years) had received IFN therapy between 2004 and 2008. Among the patients who had received IFN therapy, 2014 had received ATDs, and 8684 had not. A Cox proportional hazards regression model was applied after adjusting for age, sex, income, urbanization, medical comorbidity, and medication use. Results: Compared with non-ATD-treated patients, ATD-treated patients were more likely to receive a diagnosis of alcohol-related disease, diabetes mellitus (DM), hypertension, and hyperlipidemia. ATD-treated patients had a significantly lower incidence of HCC than non-ATD-treated patients (P = 0.0019). Female, older (age ≥50 years), and non-DM patients who had received cumulative high doses of ATDs had a significantly lower risk of HCC than non-ATD-treated patients. After adjustment, only high-dose selective serotonin reuptake inhibitor (SSRI) use was inversely associated with HCC risk (adjusted hazard ratio 0.37, 95% confidence interval 0.19–0.71, P = 0.0027). Conclusions: Our study showed that ATD use, especially a relatively high cumulative dose of SSRIs, in HCV-infected patients who had received IFN was associated with reduced HCC risk. Future clinical studies are warranted to explore the underlying mechanisms and to apply them to newer direct-acting antiviral agent treatments.

Objective: In this study, we intended to compare the insight in patients with schizophrenia (SCH), bipolar I disorder (BD), and major depressive disorder (MDD). Methods: This cross-sectional study was conducted from December 2017 to July 2018. We recruited 102 patients with SCH (n = 55), BD (n = 25), and major depression (n = 22) to assess insight with the Taiwanese version of Self-Appraisal of Illness Questionnaire (SAIQ), and to test the differences of those patient groups. Results: Patients with SCH had a significantly lower average SAIQ score compared with MDD (25.95 ± 9.70 vs. 36.38 ±7.75, p < 0.01), but no significant difference existed in patients between the SCH and bipolar disorder. For the SAIQ worry subscale, patients with SCH (p < 0.05) and those with bipolar disorder (p < 0.01) had significant lower scores than those with major depression. For the need for treatment subscale, patients with SCH had significantly lower scores than those with bipolar disorder (p < 0.05) and those with major depression (p < 0.05). For the presence/outcome of illness subscale, patients with SCH had significant lower scores than those with bipolar disorder (p < 0.01) and those with major depression (p < 0.001). Conclusion: Patients with SCH had lower total insight as well as individual domain than patients with MDD. Patients with SCH had poorer insight than those with bipolar disorder in need for treatment and presence/outcome of illness, but not in the worry subscale. The significant difference in patients with BD and those with major depression were on the worry domain.

Objective Several cell line studies have demonstrated thioridazine's anticancer, multidrug resistance-reversing and apoptosis-inducing properties in various tumors. We conducted this nationwide population-based study to investigate the association between thioridazine use and cancer risk among adult patients with schizophrenia. Methods Based on the Psychiatric Inpatient Medical Claim of the National Health Insurance Research Database of Taiwan, a total of 185,689 insured psychiatric patients during 2000 to 2005 were identified. After excluding patients with prior history of schizophrenia, only 42,273 newly diagnosed patients were included. Among them, 1,631 patients ever receiving thioridazine for more than 30 days within 6 months were selected and paired with 6,256 randomly selected non-thioridazine controls. These patients were traced till 2012/12/31 to see if they have any malignancy. Results The incidence rates of hypertension and cerebrovascular disease were higher among cases than among matched controls. The incidence of hyperlipidemia, coronary artery disease and chronic pulmonary disease did not differ between the two groups. By using Cox proportional hazard model for cancer incidence, the crude hazard ratio was significantly higher in age, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease and chronic pulmornary disease. However, after adjusting for other covariates, only age and hypertension remained significant. Thioridazine use in adult patients with schizophrenia had no significant association with cancer. Conclusion Despite our finding that thioridazine use had no prevention in cancer in adult patients with schizophrenia. Based on the biological activity, thioridazine is a potential anticancer drug and further investigation in human with cancer is warranted.

BackgroundThe decreased life expectancy and care costs of mental disorders could be enormous. However, research that compares mortality and utilization concurrently across the major category of mental disorders is absent. This study investigated all-cause mortality and medical utilization among patients with and without mental disorders, with an emphasis on identifying the psychiatric category of high mortality and low medical utilization.MethodsA total of 570,250 individuals identified from the 2002–2013 Taiwan National Health Insurance Reearch Database consistuted 285,125 psychiatric patients and 285,125 non-psychiatric peers through 1:1 dual propensity score matching (PSM). The expenditure survival ratio (ESR) was proposed to indicate potential utilization shortage. The category of mental disorders and 13 covariates were analyzed using the Cox proportional hazard model and general linear model (GLM) through SAS 9.4.ResultsPSM analyses indicated that mortality and total medical expenditures per capita were both significantly higher in psychiatric patients than those in non-psychiatric patients (allPP P P ConclusionSubstance use disorders are the category of highest YPLL but notably in insufficient utilization. Health care utilization in patients with substance use disorders should be augmented timely after the diagnosis, especially toward home and community care. The factors related to mortality and utilization identified by this study merit clinical attention.

Introduction Obstructive sleep apnea (OSA) is a serious sleep disorder characterized by repetitive episodes of paused or shallow breathing during sleep. Patients with OSA often have excessive daytime sleepiness. The role of cigarette smoking in OSA remains controversial. The aim of this study was to examine the relationship between cigarette smoking and OSA. Methods In this retrospective chart review, we reviewed 18-month sleep laboratory charts in central Taiwan. We collected data regarding sleep, current cigarette smoking status, sex, age, body mass index (BMI), neck circumference, Epworth Sleepiness Scale score, and polysomnographic sleep parameters. In total, 733 subjects were recruited; among these, 151 were smokers and 582 were nonsmokers. Results Smokers had significantly higher apnea–hypopnea index (p

Differences in child abuse perpetration between individuals with and without mental disorders remain obscure. This study compared the risk difference and further investigated the association between the category of mental disorders and child abuse perpetration. A total of 681,970 adults from the 2002 to 2013 Taiwan National Health Insurance Research Database were analyzed, including 340,985 patients with psychiatric disorders (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 290.x–319.x) and 340,985 sex- and age-matched individuals without psychiatric disorders. Child abuse perpetration (ICD-9-CM N-codes 995.5x and E-code E967) was the outcome variable. Matched analyses indicated that the risk of child abuse among patients with psychiatric disorders (0.25%) was significantly higher than that among those without psychiatric disorders (0.16%; odds ratio [OR] = 1.464, p < .0001). Among the six categories of mental disorders, the prevalence rates of committing child abuse were significantly higher for personality disorders, substance use, and affective disorders (0.56%, 0.45%, and 0.40%, respectively; p < .0001). Compared with anxiety disorders, substance use disorders were significantly associated with higher odds of child abuse perpetration (OR = 2.032, p < .05), especially physical abuse (OR = 2.018, p < .0001). Psychiatric morbidity was associated with higher odds of child abuse, with substance use determined as the major risk category. Screening high-risk families by using the associated factors is crucial.

Depression causes sleep disturbance and is associated with various sleep-related disorders. However, how depression affects the symptomatic presentation of different sleep-related disorders is unclear. In this study, we investigated the sleep parameters of different sleep-related disorders between depressive and non-depressive patients. A total of 785 patients underwent polysomnography in a mental hospital from Jan 2012 to Jun 2013. We first analyzed variables between the depressive and non-depressive groups. The patients were then divided into four groups: obstructive sleep apnea (OSA, n = 339), restless leg syndrome (RLS, n = 51), periodic limb movement disorder (PLMD, n = 58) and comorbid group (OSA and RLS, n = 46). We next compared sleep measures between the depressive and non-depressive subjects within each groups. The patients with OSA and depression were significantly associated with a higher periodic limb movement index. Significantly more patients with RLS patients and depression had initial insomnia complaints. However, significantly more patients with PLMD and depression middle insomnia. Compared with non-depressive population, depressive patients had higher comorbidity with RLS and PLMD. Depression may have different association with the sleep parameters in different sleep-related disorders. Further investigations are needed to investigate how these findings may affect patients' awareness and clinicians' diagnosis and management of sleep-related disorders.

Delirium is common in daily practice. Drug-induced delirium constitutes approximately one-third of all cases of delirium. In cases characterized by the limited efficacy of a single antidepressant, a combination of two antidepressants is required, which may induce a complex drug-drug interaction. We reviewed a case of duloxetine- and bupropion-related delirium in an elderly male patient in our clinical practice. The patient was diagnosed with major depressive disorder and was treated with duloxetine. However, he developed delirium 10 days after bupropion was added to his treatment regimen. Three days after the cessation of bupropion, his delirious condition gradually improved. Duloxetine and bupropion are both cytochrome P450 2D6 inhibitors that may result in a higher level of hydroxybupropion. An increased level of hydroxybupropion may cause the elevation of dopamine and a risk of subsequent delirium. We should be aware of the risk of delirium induced by drug-drug interactions.

Aim The aim of this study was to compare alterations of mitochondrial DNA (mtDNA) copy number, single nucleotide polymorphisms, and oxidative damage of mtDNA in clinically stable patients with bipolar I disorder (BD). Methods Patients meeting DSM-IV diagnostic criteria for BD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding 2 months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any history of major psychiatric disorders and they were non-smokers. By analyzing peripheral blood leukocytes, copy number, single nucleotide polymorphisms and oxidative damage of mtDNA were compared between the two groups. Results The median age of the subjects was 38 years and 41.5 years in the comparison and BD groups, respectively. The leukocyte mtDNA copy number of the BD group was significantly lower than that of the comparison group (P

Major depressive disorder (MDD), the most prevalent mental disorder is a global public health issue. The aim of this study was to assess the association between low income and major depressive disorder (MDD) by age and sex. The National Health Insurance Research Database (NHIRD) of Taiwan was used to retrieve data. A total of 1,743,948 participants were eligible for the study. Low-income individuals were identified from 2001 and 2003 (specifically, Group Insurance Applicants, ie, category"51" or "52") and followed from 2004 to 2010. MDD was identified using the ICD-9-CM 296.2 and 296.3 codes. Among non-low-income individuals, the MDD incidence rates increased with age in both males and females, that is, 0.35, 0.93, 0.97, 1.40 per 10,000 person-months for males and 0.41, 1.60, 1.89, 1.95 per 10,000 person-months for females aged 0 to 17, 18 to 44, 45 to 64, and ≥65 years, respectively. Low-income females (18-44 years) and males (45-64 years) had the highest incidence of MDD, which was 3.90 and 3.04, respectively, per 10,000 person-months. Among low and non-low-income individuals, the MDD incidence rates were higher in the females than males in all age groups. Males aged 45 to 64 and 0 to 17 years had highest hazard ratios (HR) of 2.789 (95% confidence interval [CI], 1.937-4.014) and 2.446 (95% CI, 1.603-3.732), respectively. The highest HRs for females were 2.663 (95% CI, 1.878-3.775) and 2.219 (CI, 1.821-2.705) in the 0 to 17 and 18- to 44-year age groups. Low income was not found to serve as a risk factor for the development of MDD in males and females aged ≥65 years. Among the non-low-income males and females, the incidence rates of MDD were found to increase with age. Low income was found to serve as a significant risk factor for MDD only in individuals under age 65.

Catatonia is a clinical syndrome consisting of catalepsy and waxy flexibility, mutism, rigidity, negativism, and stereotypy. It was first described by Kahlbaum and then considered as a purely psychiatric condition. Although commonly associated with schizophrenia upon influences of Kraepelin and Bleuler, there were several reports associating catatonia and mood disorders as well as general medical conditions. Benzodiazepine withdrawal and alcohol withdrawal induced catatonia have been previously reported in the literature. Here, we present a case of catatonia that occurred after zolpidem withdrawal.

OBJECTIVE This study aims to investigate association between early recognizable minor physical abnormality (MPA) during childhood is associated with mental health problems in young adults. METHODS In 1984, 169 preschool children in central Taiwan underwent a detailed physical examination for subtle abnormalities (MPA). Fourteen years later, the Brief Symptom Rating Scale (BSRS) and Chinese Health Questionnaire (CHQ) were used to measure specific psychiatric symptoms. RESULTS There is an association between MPA during childhood and adult characterized with interpersonal sensitivity, anxiety, depression and paranoid mental health symptoms. CONCLUSION The signs of childhood MPA can be easily identified and should be regarded as risk factors when predicting mental disorder. Mental health professionals should consider MPAs as important signs for possible development of emotional problems.

To the Editor: Spinocerebellar ataxia (SCA) is an inherited disorder of brain function characterized by progressive incoordination of gait and is often associated with poor coordination of hands, speech, and eye movements. It is a slowly progressive disease that gradually worsens over a period of years. Zolpidem is a nonbenzodiazepine sedative in the imidazopyridine class and is chemically distinct from other sedatives. It is a short-acting hypnotic with a selective agonist effect for γ-aminobutyric acid (GABA) type A receptors in the brain. It was considered originally by physicians as almost devoid of abuse and dependence potential. Intriguingly, aside from its hypnotic effect, zolpidem has been shown to improve catatonia,1 aphasia,2 Parkinson's disease,3 and ataxia.4 However, reports of zolpidem abuse or dependence are increasing,5,6 and more attention should be paid in terms of zolpidem withdrawal. We report a patient with SCA who took zolpidem for movement difficulties initially, developed dependence on high-dose zolpidem treatment, and encountered serious withdrawal symptoms. We also review the literature on the possible mechanism for the effect of zolpidem on SCA. Case report. Ms A, a 40-year-old married woman, was referred in 2009 for psychiatric consultation due to high-dose zolpidem use. She was diagnosed with SCA type IV at age 35 years with initial symptoms of unsteady gait and mild slurred speech. Her father and brother were also afflicted with SCA. This time, she was admitted via emergency department to our neurology department because of loss of consciousness. Generalized seizure lasted for 1 minute at home, and initial management at the emergency department with phenytoin intravenous drip terminated further progression. Toxicology testing detected no plasma alcohol, whereas plasma benzodiazepine level was 64.80 ng/mL. She claimed she had abused triazolam and alcohol during early adulthood due to insomnia. Other illicit substance use was denied. She had started taking zolpidem 3 years earlier for insomnia, and, paradoxically, zolpidem relieved her ataxia and spasticity. She recalled being able to move her arms and turn her trunk more easily, although the improvement lasted only around 1 hour after taking zolpidem. The dose of zolpidem was gradually escalated by the patient to reach optimal effect. The dose usually amounted to 1,000 mg/d for the past year. Nausea, palpitation, jitters, hand tremor, and perspiration were noted if she did not take enough zolpidem. She was bedridden due to SCA and was cared for by her husband. Although she consumed high doses of zolpidem, her husband tried to cater to all her needs out of sympathy. Zolpidem had been prescribed from different physicians. Withdrawal seizures were noted several times if her supply of zolpidem fell short. Ms A was detoxified by taper of zolpidem gradually over 2 weeks. We prescribed trazodone 100 mg before sleep and diazepam 20 mg/d and propranolol 30 mg/d for anxiety. No seizure attack was noted during hospitalization. After this 2-week hospitalization, she was referred to the psychiatric clinic for further management. The imidazopyridine hypnotic zolpidem binds preferably to the α1 subtype of the benzodiazepine receptor, which is part of GABAA receptor complex. This highly accounts for its sedative effect, whereas the anxiolytic action of benzodiazepines appears to be mediated by receptors that contain the α2 subunit.7 Zolpidem at high doses might lose its selectivity on α1 subunits and bind to lower-affinity α2 units, leading to an anxiolytic effect. Thus, high-dose zolpidem may have a paradoxical effect for alleviating anxiety, and abrupt discontinuation would produce withdrawal symptoms such as palpitation, anxiety, tremor, or seizure similar to those seen with benzodiazepine withdrawal. There is no definite treatment that can prevent or slow the progression of SCA. Clauss et al4 reported transient improvement of SCA with zolpidem in 4 cases. Single photon emission computed tomography demonstrated that GABAergic function may be decreased in the cerebral cortex, thalamus, striatum, and cerebellum in patients with SCA.8 Zolpidem has been shown to mildly improve catatonia, aphasia, and Parkinson's disease.9 Such motor improvement may be due to selective inhibition by zolpidem of GABAergic inhibitory neurons in the internal globus pallidus and substantia nigra pars reticulata, resulting in activation of the thalamus and cerebral cortex.9 Positron emission tomography imaging also has shown normalized tracer uptake in the left thalamus and cerebellum after treatment with zolpidem.4 Our case further corroborates that zolpidem has a mode of action apart from hypnotic properties. To our knowledge, this is the first case report concerning high-dose zolpidem withdrawal seizure in a patient with SCA. We should be more cautious in prescribing zolpidem to patients with past drug abuse or dependence to prevent unwanted consequence. Further investigation of the pharmacologic efficacy of zolpidem in SCA might be needed.