Delayed effect of bifrontal transcranial direct current stimulation in patients with treatment-resistant depression: a pilot study.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique, which has yielded promising results in treating major depressive disorder. However, its effect on treatment-resistant depression remains to be determined. Meanwhile, as an emerging treatment option, patients' acceptability of tDCS is worthy of attention. METHODS: This pilot study enrolled 18 patients (women = 13) with treatment-resistant unipolar (n = 13) or bipolar (n = 5) depression. Twelve sessions of tDCS were administered with anode over F3 and cathode over F4. Each session delivered a current of 2 mA for 30 min per ten working days, and at the 4th and 6th week. Severity of depression was determined by Montgomery-Åsberg Depression Rating Scale (MADRS); cognitive performance was assessed by a computerized battery. RESULTS: Scores of MADRS at baseline (29.6, SD = 9.7) decreased significantly to 22.9 (11.7) (p = 0.03) at 6 weeks and 21.5 (10.3) (p = 0.01) at 8 weeks. Six (33.3%) participants were therapeutically responsive to tDCS. MADRS scores of responders were significantly lower than those of non-responders at the 6th and 8th week. Regarding change of cognitive performance, improved accuracy of paired association (p = 0.017) and social cognition (p = 0.047) was observed at the 8th week. Overall, tDCS was perceived as safe and tolerable. For the majority of patients, it is preferred than pharmacotherapy and psychotherapy. CONCLUSIONS: TDCS can be a desirable option for treatment-resistant depression, however, its efficacy may be delayed; identifying predictors of therapeutic response may achieve a more targeted application. Larger controlled studies with optimized montages and sufficient periods of observation are warranted. TRIAL REGISTRATION: This trial has been registered at the Chinese Clinical Trial Registry ( ChiCTR-INR-16008179 ).

Excess incidence and risk factors for recurrent pneumonia in bipolar disorder.

AIM: Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD. METHODS: In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk-set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs. RESULTS: The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person-years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first- and second-generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence. CONCLUSION: We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre-existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia.

Antipsychotic drugs and risk of newly diagnosed tuberculosis in schizophrenia.

AIM: Patients with schizophrenia have a higher incidence of tuberculosis than do people in the general population. Information is limited regarding the association between antipsychotic agents and the risk of tuberculosis in patients with schizophrenia. This exploratory study assessed the risk of tuberculosis among patients with schizophrenia on antipsychotic therapy. METHODS: Among a nationwide schizophrenia cohort derived from the National Health Insurance Research Database in Taiwan (n = 32 399), we identified 284 patients who had developed newly diagnosed tuberculosis after their first psychiatric admission. Ten or fewer matched controls were selected randomly from the cohort for each patient based on risk-set sampling. We categorized exposure to antipsychotic medications by type and defined daily dose. Using multivariate methods, we explored individual antipsychotic agents for the risk of tuberculosis and employed a propensity-scoring method in sensitivity analyses to validate any associations. RESULTS: Among the antipsychotic agents studied and after adjustment for covariates, current use of clozapine was the only antipsychotic agent associated with a 63% increased risk of tuberculosis (adjusted risk ratio = 1.63, P = 0.014). In addition, the association did not show a clear dose-dependent relationship. Clozapine combined with other antipsychotic agents showed a potential synergistic risk for tuberculosis (adjusted risk ratio = 2.30, P = 0.044). CONCLUSION: This exploratory study suggests the potential risk of clozapine on the risk of tuberculosis, especially for those on clozapine in combination with other antipsychotics. Future studies are needed to verify the association.

Cognitive ability in childhood and the chronicity and suicidality of depression.

BACKGROUND: There is inconsistent evidence regarding the influence of general cognitive abilities on the long-term course of depression. AIMS: To investigate the association between general childhood cognitive abilities and adult depression outcomes. METHOD: We conducted a cohort study using data from 633 participants in the New England Family Study with lifetime depression. Cognitive abilities at age 7 were measured using the Wechsler Intelligence Scale for Children. Depression outcomes were assessed using structured diagnostic interviews administered up to four times in adulthood between ages 17 and 49. RESULTS: In analyses adjusting for demographic factors and parental psychiatric illness, low general cognitive ability (i.e. IQ<85 v. IQ>115) was associated with recurrent depressive episodes (odds ratio (OR) = 2.19, 95% CI 1.20-4.00), longer episode duration (rate ratio 4.21, 95% CI 2.24-7.94), admission to hospital for depression (OR = 3.65, 95% CI 1.34-9.93) and suicide ideation (OR = 3.79, 95% CI 1.79-8.02) and attempt (OR = 4.94, 95% CI 1.67-14.55). CONCLUSIONS: Variation in cognitive abilities, predominantly within the normal range and established early in childhood, may confer long-term vulnerability for prolonged and severe depression. The mechanisms underlying this vulnerability need to be established to improve the prognosis of depression among individuals with lower cognitive abilities.

Effect of media reporting of the suicide of a singer in Taiwan: the case of Ivy Li.

BACKGROUND: Suicide attempters are known to be vulnerable to the influence of media reporting of suicide events. This study investigates possible influences of media reporting of a celebrity suicide on subsequent suicide attempts and associated risk factors among suicide attempters. METHODS: Sixty-three suicide attempters registered in a surveillance system of Taipei City Suicide Prevention Center were assessed using a structured interview soon after media reporting of the suicide of a young female singing star. RESULTS: Forty-three (68%) respondents had encountered with the suicide news. Among them, 37% reported being influenced by the media reporting on their subsequent suicide attempts. Men (adjusted OR 6.36, 95% CI 1.29-31.44) and younger age groups (adjusted OR 4.93, 95% CI 1.04-23.45) were more susceptible to the media reporting. There was a positive modeling effect in method of suicide (charcoal burning) (adjusted OR 7.27, 95% CI 6.31-168.66). CONCLUSIONS: This study has provided further evidence for suicide imitation among vulnerable people encountered with media reporting of celebrity suicide, and for the need to actively restrain reporting of suicides to decrease the imitation effect.

Searching for suicide-related information on Chinese websites.

Growing concerns about cyber-suicide have prompted many studies on suicide information available on the web. However, very few studies have considered non-English websites. We aimed to analyze online suicide-related information accessed through Chinese-language websites. We used Taiwan's two most popular search engines (Google and Yahoo) to explore the results returned from six suicide-related search terms in March 2016. The first three pages listing the results from each search were analyzed and rated based on the attitude towards suicide (pro-suicide, anti-suicide, neutral/mixed, not a suicide site, or error). Comparisons across different search terms were also performed. In all, 375 linked webpages were included; 16.3% of the webpages were pro-suicide and 41.3% were anti-suicide. The majority of the pro-suicide sites were user-generated webpages (96.7%). Searches using the keywords 'ways to kill yourself' (31.7%) and 'painless suicide' (28.3%) generated much larger numbers of harmful webpages than the term 'suicide' (4.3%). We conclude that collaborative efforts with internet service providers and search engines to improve the ranking of anti-suicide webpages and websites and implement online suicide reporting guidelines are highly encouraged.

Predicting Negative Emotions Based on Mobile Phone Usage Patterns: An Exploratory Study.

BACKGROUND: Prompt recognition and intervention of negative emotions is crucial for patients with depression. Mobile phones and mobile apps are suitable technologies that can be used to recognize negative emotions and intervene if necessary. OBJECTIVE: Mobile phone usage patterns can be associated with concurrent emotional states. The objective of this study is to adapt machine-learning methods to analyze such patterns for the prediction of negative emotion. METHODS: We developed an Android-based app to capture emotional states and mobile phone usage patterns, which included call logs (and use of apps). Visual analog scales (VASs) were used to report negative emotions in dimensions of depression, anxiety, and stress. In the system-training phase, participants were requested to tag their emotions for 14 consecutive days. Five feature-selection methods were used to determine individual usage patterns and four machine-learning methods were tested. Finally, rank product scoring was used to select the best combination to construct the prediction model. In the system evaluation phase, participants were then requested to verify the predicted negative emotions for at least 5 days. RESULTS: Out of 40 enrolled healthy participants, we analyzed data from 28 participants, including 30% (9/28) women with a mean (SD) age of 29.2 (5.1) years with sufficient emotion tags. The combination of time slots of 2 hours, greedy forward selection, and Naïve Bayes method was chosen for the prediction model. We further validated the personalized models in 18 participants who performed at least 5 days of model evaluation. Overall, the predictive accuracy for negative emotions was 86.17%. CONCLUSION: We developed a system capable of predicting negative emotions based on mobile phone usage patterns. This system has potential for ecological momentary intervention (EMI) for depressive disorders by automatically recognizing negative emotions and providing people with preventive treatments before it escalates to clinical depression.

Delayed effect of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia: Findings from a randomized controlled trial.

Evidence is inconsistent regarding the effect of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia. In this study, 47 patients were randomized to receive either active rTMS over left dorsolateral prefrontal cortex (n=25) or sham stimulation (n=22). Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS) at baseline, 4 weeks and 8 weeks. At 4 weeks, there was no difference in SANS scores between 2 groups. By 8 weeks, patients with active rTMS had significantly reduced SANS score than controls. Our findings suggest a delayed effect of rTMS on negative symptoms.

Smartphone-based ecological momentary assessment for Chinese patients with depression: An exploratory study in Taiwan.

Mobile mental health has a potential to improve the recognition and management of Chinese patients with depression. Currently, evidence regarding ecological momentary assessment (EMA) for depressive disorder mostly originates from Western studies. Herein, we examined the validity of smartphone-based EMA for depression in Chinese patients and explored the determinants of use. A smartphone application, iHOPE, was used to perform daily EMA of depression, anxiety, sleep and cognitive performance. Outpatients with depressive disorder were recruited to use iHOPE for 8 weeks. Clinical characteristics and smartphone use patterns were assessed at baseline. We enrolled 59 Chinese patients with depression. In 8 weeks, participants interacted with iHOPE for an average of 10.8 (SD=12.3) days; a trend of decreased frequency of use (p=0.03) was observed. Scores of HAM-D at baseline was associated with, of the first 2 weeks, scores of PHQ-9 (p=0.005), EMA of depression (p=0.003) and anxiety (p<0.001), and poorer sleep quality (p=0.023). Among the demographic, clinical and smartphone-use variables examined, only limited internet package for smartphone (<500M per month) predicted higher use of iHOPE (p=0.04). The present study provides initial evidence for the feasibility of smartphone-based EMA in Chinese patients with depression. Level of engagement needs to be improved before determining its clinical usefulness.

Antipsychotic reexposure and recurrent pneumonia in schizophrenia: a nested case-control study.

OBJECTIVE: Few studies have used systematic datasets to assess the safety of antipsychotic rechallenge after an adverse event. This nested case-control study estimated the risk for recurrent pneumonia after reexposure to antipsychotic treatment. METHOD: In a nationwide schizophrenia (ICD-9-CM code 295) cohort (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia (ICD-9-CM codes 480-486, 507) between 2000 and 2008 (N = 2,201), we identified 494 subjects that developed recurrent pneumonia after a baseline pneumonia episode. Based on risk-set sampling in a 1:3 ratio, 1,438 matched controls were selected from the cohort. Exposures to antipsychotics were categorized by type, duration, and defined daily dose. Using propensity score-adjusted analysis, we assessed individual antipsychotics for the risk of recurrent pneumonia; we furthermore assessed the effect of reexposure to these antipsychotics on the risk of recurrent pneumonia. RESULTS: Of the antipsychotics studied, current use of clozapine was the only one associated with a clear dose-dependent increase in the risk for recurrent pneumonia (adjusted risk ratio = 1.40, P = .024). Intriguingly, patients reexposed to clozapine had a higher risk for recurrent pneumonia (adjusted risk ratio = 1.99, P = .023) than those receiving clozapine only prior to the baseline pneumonia, and this risk was associated with gender. Women reexposed to clozapine were more susceptible to recurrent pneumonia (adjusted risk ratio = 4.93, P = .050). CONCLUSIONS: In patients experiencing pneumonia while undergoing clozapine treatment, physicians should carefully consider the increased risk of pneumonia recurrence when clozapine is reintroduced. Future studies should try to quantify the risk of other medical conditions associated with clozapine reexposure.

Predicting suicide in older adults - a community-based cohort study in Taipei City, Taiwan.

BACKGROUND: Older adults worldwide are at a greater risk of suicide than other age groups. There is a scarcity of prospective studies exploring risk factors for suicide in older people and their discriminative ability to identify future suicide. METHODS: We examined a prospective cohort of senior Taipei City residents between 2005 and 2009 (N=101,764). Cox proportional hazards regression analysis was used to determine significant risk factors and to construct a predictive score. The accuracy of the derived score in the prediction was tested by Receiver Operating Characteristic analysis. RESULTS: Male sex (Hazard Ratio [HR]=3.41, p<0.001), lower education (HR=3.31, p<0.001) and lower income (HR=2.52, p=0.01) were associated with an increased risk of suicide, as well as depressed mood (HR=1.44, p=0.02; per unit increase in a 4-point scale) and insomnia (HR=1.30, p=0.03; per unit increase in a 4-point scale). The derived prediction score yielded a sensitivity of 0.63 a specificity of 0.73 and an area under curve of 0.73. Removing depressed mood from the prediction model did not significantly alter suicide predictability (P=0.11). LIMITATIONS: The dataset examined did not contain information regarding to important risk factors such as substance misuse and prescribed medications and the measures of mental health were relatively limited. CONCLUSION: Prediction of suicide based on factors recorded in a routine health screen of elderly people was unsatisfactory; the strongest predictors were factors that cannot be easily altered. Further understanding of how the socioeconomic condition of seniors contributes to suicide may provide valuable insights for intervention targeting this growing population-at-risk.

Illness beliefs of Chinese American immigrants with major depressive disorder in a primary care setting.

Underutilization of mental health services in the U.S. is compounded among racial/ethnic minorities, especially Chinese Americans. Culturally based illness beliefs influence help-seeking behavior and may provide insights into strategies for increasing utilization rates among vulnerable populations. This is the first large descriptive study of depressed Chinese American immigrant patients' illness beliefs using a standardized instrument. 190 depressed Chinese immigrants seeking primary care at South Cove Community Health Center completed the Explanatory Model Interview Catalogue, which probes different dimensions of illness beliefs: chief complaint, labeling of illness, stigma perception, causal attributions, and help-seeking patterns. Responses were sorted into categories by independent raters and results compared to an earlier study at the same site and using the same instrument. Contrary to prior findings that depressed Chinese individuals tend to present with primarily somatic symptoms, subjects were more likely to report chief complaints and illness labels related to depressed mood than physical symptoms. Nearly half reported they would conceal the name of their problem from others. Mean stigma levels were significantly higher than in the previous study. Most subjects identified psychological stress as the most likely cause of their problem. Chinese immigrants' illness beliefs were notable for psychological explanations regarding their symptoms, possibly reflecting increased acceptance of Western biomedical frameworks, in accordance with recent research. However, reported stigma regarding these symptoms also increased. As Asian American immigrant populations increasingly accept psychological models of depression, stigma may become an increasingly important target for addressing disparities in mental health service utilization.

Risk and protective factors for suicide mortality among patients with alcohol dependence.

OBJECTIVE: People with alcohol dependence suffer from poor health outcomes, including excessive suicide mortality. This study estimated the suicide rate and explored the risk and protective factors for suicide in a large-scale Asian population. METHOD: We enrolled patients with alcohol dependence (ICD-9 code 303**) consecutively admitted to a psychiatric center in northern Taiwan from January 1, 1985, through December 31, 2008 (N = 2,793). Using patient linkage to the national mortality database (1985-2008), we determined that 960 patients died during the study period. Of those deaths, 65 patients died of suicide. On the basis of risk-set sampling for the selection of controls, we conducted a nested case-control study and collected the information by means of a standardized chart review process. We estimated the standardized mortality ratio (SMR) for suicide mortality. Conditional logistic regression was employed for exploring the risk and protective factors for suicide. RESULTS: The study subjects had excessive suicide and all-cause deaths, with SMRs of 21.2 and 12.7, respectively. We pinpointed auditory hallucination (adjusted risk ratio [aRR] = 1.80, P = .04) and attempted suicide (aRR = 7.52, P = .001) as the risk factors associated with suicide. In contrast, protective factors included financial independence (aRR = 0.11, P = .005) and being married (aRR = 0.16, P = .02). Intriguingly, those with physical illnesses had a lower risk of suicide (aRR = 0.15, P = .01). CONCLUSIONS: Compared with the general population, those with alcohol dependence faced excessive suicide mortality. For a comprehensive approach to suicide prevention, recognizing and improving the protective factors could have equal importance in mitigating the risk of suicide.

Risk factors for sudden cardiac death among patients with schizophrenia.

INTRODUCTION: Patients with schizophrenia suffer from excessive premature mortality, and sudden cardiac death (SCD) is receiving growing attention as a potential cause. AIM: The present study investigated the incidence of SCD and its risk factors in a large schizophrenia cohort. METHODS: We enrolled a consecutive series of 8264 patients diagnosed with schizophrenia (according to DSM-III-R and DSM-IV criteria) who were admitted to a psychiatric center in northern Taiwan from January 1, 1985 through December 31, 2008. By linking with national mortality database, 64 cases of SCD were identified. The standardized mortality ratio (SMR) for SCD was estimated. The cases were matched with controls randomly selected using risk-set sampling in a 1:2 ratio. A standardized chart review process was used to collect socio-demographic and clinical characteristics and the prescribed drugs for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of SCD at the index admission and the latest admission. RESULTS: The SMR for SCD was 4.5. For the clinical profiles at the index admission, physical disease (adjusted risk ratio [aRR]=2.91, P<.01) and aggressive behaviors (aRR=3.99, P<.01) were associated with the risk of SCD. Regarding the latest admission, electrocardiographic abnormalities (aRR=5.46, P<.05) and administration of first-generation antipsychotics (aRR=5.13, P<.01) elevated the risk for SCD. Consistently, aggressive behaviors (aRR=3.26, P<.05) were associated with increased risk as well. CONCLUSIONS: Apart from cardiovascular profiles and antipsychotics, physical aggression is a crucial risk factor that deserves ongoing work for clarifying the mechanisms mediating SCD in schizophrenia.

Psychotropic polypharmacy for the treatment of bipolar disorder in Taiwan.

OBJECTIVE: Psychotropic polypharmacy in the treatment of bipolar disorder has proliferated. Yet evidence about the prevalence and predictors of different combinations of polypharmacy in inpatient settings is scarce. METHODS: The Nationwide Psychiatric Inpatient Medical Claims (2000-2007) in Taiwan were used to examine prescriptions for mood stabilizers, antipsychotics, and antidepressants among recently discharged patients with bipolar disorder (N=5,449; 51% women, mean±SD age=36.8±12.4). RESULTS: A total of 71% of prescriptions involved between-class polypharmacy, and 17% involved within-class polypharmacy. Patients older than 50 and patients at medical centers (>500 beds) were less likely to receive polypharmacy. Lower prescribed doses predicted polypharmacy. Receiving polypharmacy was not associated with a higher rate of readmission within one year. CONCLUSIONS: There was substantial use of various forms of polypharmacy in the treatment of inpatients with bipolar disorder. Randomized studies should be used to compare the cost-effectiveness of common psychotropic combinations and monotherapy to treat bipolar disorder.

Predicting suicide attempts among treatment-seeking male alcoholics: an exploratory study.

Documented risk factors for suicide among alcohol-dependent patients are sensitive but insufficiently specific to effectively identify individuals who are prone to future suicide attempt. As a first step to assess factors not previously considered, this pilot study involved a group of male alcohol-dependent patients (N = 175) coming to detoxification to examine the potential utility of adverse childhood experiences (ACE) along with other documented events to discriminate individuals with a history of attempted suicide from their detoxifying peers. Family health history questionnaires were used to evaluate their ACEs. Receiver operating characteristic (ROC) analysis was applied to examine the predictive power of ACEs, alone or in combination with documented risk factors, to lifetime history of attempted suicide. Among our participants, 48 (27.4%) had a history of a suicide attempt and 156 (89.1%) reported at least one out of the nine categories of ACEs. Modeling by ROC analysis, we found that a cutoff of four or more ACEs plus a history of personal violence achieved the best predictive power to a history of any suicide attempt, producing a sensitivity of 0.7, specificity of 0.81, and area under curve of 0.75. A prospective study to replicate and extend our findings is necessary.

Association between childhood adversities and suicide attempts among alcoholic inpatients in Taiwan.

OBJECTIVE: Alcohol dependence is frequently associated with suicide attempts. A history of adverse childhood experiences (ACEs) increases the risk of emotional and behavioral problems in adulthood. Child abuse is reported to increase suicide risk among alcohol-dependent patients. However, other types of ACEs, including ACEs related to family dysfunction that may have exceptional impact among the Chinese, are rarely explored. METHOD: The contribution of a broad spectrum of ACEs to lifetime risk of suicide attempts among alcoholic inpatients in Taiwan was examined. Family Health History Questionnaires were used to assess ACEs among 194 male alcohol-dependent inpatients admitted for alcohol detoxification. Logistic regression analysis was applied to examine the prediction of ACEs for lifetime risk of suicide attempts. RESULTS: The rate of attempted suicide in this cohort was 27.4%. The prevalence of ACEs was high, with around 90% of participants reporting at least one type of ACE. In the regression analysis, after adjusting for lifetime depression, illicit drug use, and severity of alcohol dependence, having had a battered mother (odds ratio [OR] = 3.99, 95% CI [1.40, 11.34]) and having parents who were separated/divorced (OR = 7.35, 95% CI [1.56, 34.72]) were associated with the risk of suicide attempts, but having experienced physical and sexual abuse were not. A 1-unit increase in childhood adversity raised the likelihood of a suicide attempt by 61% (OR = 1.61, 95% CI [1.16, 2.25]). CONCLUSIONS: There is a direct and graded relationship between childhood adversities and lifetime risk of suicide attempts among male alcoholic patients. In Chinese societies, adversities related to parental separation, divorce, and interparental violence may have a specific effect in aggravating suicide risk.