Nian-Sheng Tzeng

A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

Background: Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Methods: Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Results: After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. Conclusions: We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT.

Internalized Stigma and Stigma Resistance Among Patients with Mental Illness in Han Chinese Population

Research suggests that accurate measurement is essential in evaluating internalized stigma and abilities to combat with stigma for treatment compliances and outcomes in individuals with mental illness. The purpose of this study was to assess the reliability and validity of the Chinese version of the Internalized Stigma of Mental Illness Scale (ISMIS-C), which is one of the few tools available to measure internalized stigma and stigma resistance (SR) simultaneously. A total of 160 outpatients with (nxa0=xa0103) and without (nxa0=xa057) psychotic disorders were administrated with the ISMIS-C, and measures of self-esteem, self-efficacy, depression, and hopelessness. Overall, the 29-item ISMIS-C was presented to be internal reliable (Cronbach’s alphaxa0=xa00.90), and reliable over time (intraclass correlation coefficientsxa0=xa00.36–0.73). The construct validity of the ISMIS-C derived from the factor analysis was nearly identical to the original version. ISMIS-C dimension scores were well correlated with each other and measures of self-esteem, self-efficacy, depression, and hopelessness. Our data also demonstrated that psychotic patients experienced higher internalized stigma scores than those without psychotic diagnoses, but endorsed indifferently on SR scores. This scale can be used as an informative device when investigating “internalized stigma” and “SR” among individuals with or without psychotic disorders.

The effects of add-on low-dose memantine on cytokine levels in bipolar II depression: a 12-week double-blind, randomized controlled trial.

Abstract Memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist with a mood-stabilizing effect, and an association between bipolar disorder and proinflammatory cytokine levels have been reported. Whether adding-on memantine would reduce cytokine levels and is more effective than valproic acid (VPA) alone in bipolar II disorder was investigated. A randomized, double-blind, controlled, 12-week study was conducted. Patients undergoing regular VPA treatments were randomly assigned to a group: VPA + memantine (5 mg/d) (n = 106) or VPA + placebo (n = 108). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response. Symptom severity, plasma tumor necrosis factor &agr; (TNF-&agr;), interleukin 6 (IL-6), IL-8, and IL-1 levels were examined during weeks 0, 1, 2, 4, 8, and 12. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Tumor necrosis factor &agr; levels were significantly lower in the VPA + memantine group than in the VPA + placebo group (P = 0.013). Posttreatment HDRS and YMRS scores decreased significantly in both groups, but not significant, nor was the other between-group cytokine level difference pretreatment and posttreatment. The HDRS score changes were significantly associated with IL-6 (P = 0.012) and IL-1 (P = 0.005) level changes and changes in YMRS score changes with TNF-&agr; (P = 0.005) level changes. Treating bipolar II depression with VPA + memantine may improve the plasma TNF-&agr; level. However, adding-on memantine may not improve clinical symptoms or cytokine levels other than TNF-&agr;. Clinical symptoms may be correlated with certain cytokines.

Heart rate variability in unmedicated patients with bipolar disorder in the manic phase

Decreased heart rate variability (HRV) has been proposed in bipolar disorder. To date, there has been no adequate study that has investigated resting HRV in unmedicated patients with bipolar disorder in the manic state.

Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: Findings from the Taiwan Study of Depression and Anxiety (TAISDA)

Evidence from previous studies suggests that heart rate variability (HRV) is reduced in major depressive disorder (MDD). However, whether this reduction is attributable to the disorder per se or to medication, since antidepressants may also affect HRV, is still debated. There is a dearth of information regarding the effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated whether HRV is reduced in MDD and compared the effects of agomelatine and paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with MDD and 506 healthy volunteers aged 20-65 years. Frequency-domain measures of resting HRV were obtained at the time of enrollment for all participants. For patients with MDD, these measures were obtained again after 6 weeks of either agomelatine or paroxetine monotherapy. Compared with healthy subjects, unmedicated patients with MDD exhibited significantly lower variance (total HRV), low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio. Depression severity independently contributed to decreased HRV and vagal tone. Fifty-six patients completed the open-label trial (n=29 for agomelatine, n=27 for paroxetine). Between-group analyses showed a significant group-by-time interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only after agomelatine treatment. Within the paroxetine-treated group, there were no significant changes in mean R-R intervals or any HRV indices. We therefore concluded that MDD is associated with reduced HRV, which is inversely related to depression severity. Compared with paroxetine, agomelatine has a more vagotonic effect, suggesting greater cardiovascular safety. Clinicians should consider HRV effects while selecting antidepressants especially for depressed patients who already have decreased cardiac vagal tone.

Correlation of plasma brain-derived neurotrophic factor and metabolic profiles in drug-naïve patients with bipolar II disorder after a twelve-week pharmacological intervention

Brain‐derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We investigated the correlation between plasma BDNF with mood symptoms and metabolic indices in patients with BD‐II over a 12‐week pharmacological intervention.

Bronchial asthma is associated with increased risk of chronic kidney disease.

BackgroundBronchial asthma influences some chronic diseases such as coronary heart disease, diabetes mellitus, and hypertension, but the impact of asthma on vital diseases such as chronic kidney disease is not yet verified. This study aims to clarify the association between bronchial asthma and the risk of developing chronic kidney disease.MethodsThe National Health Research Institute provided a database of one million random subjects for the study. A random sample of 141 064 patients aged ≥18xa0years without a history of kidney disease was obtained from the database. Among them, there were 35 086 with bronchial asthma and 105 258 without asthma matched for sex and age for a ration of 1:3. After adjusting for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing chronic kidney disease during a three-year follow-up period.ResultsOf the subjects with asthma, 2 196 (6.26%) developed chronic kidney disease compared to 4 120 (3.91%) of the control subjects. Cox proportional hazards regression analysis revealed that subjects with asthma were more likely to develop chronic kidney disease (hazard ratio [HR]: 1.56; 95% CI: 1.48-1.64; pu2009<u20090.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, diabetes mellitus, hypertension, hyperlipidemia, and steroid use, the HR for asthma patients was 1.40 (95% CI: 1.33-1.48; pu2009=u20090.040). There was decreased HRs in steroid use (HR: 0.56; 95% CI: 0.62-0.61; pu2009<u20090.001) in the development of chronic kidney disease. Expectorants, bronchodilators, anti-muscarinic agents, airway smooth muscle relaxants, and leukotriene receptor antagonists may also be beneficial in attenuating the risk of chronic kidney disease.ConclusionsPatients with bronchial asthma may have increased risk of developing chronic kidney disease. The use of steroids or non-steroidal drugs in the treatment of asthma may attenuate this risk.

Relationships of perceived public stigma of mental illness and psychosis-like experiences in a non-clinical population sample

PurposeStudies on the association between psychopathology, perceived public stigma, and labeling in mental illness have focused primarily on severe but rare mental disorders, especially schizophrenia, or other clinically defined psychotic disorders. Although evidence is mounting that psychosis-like experiences show high prevalence in the general population and lead to an increased risk of psychotic disorders, little is known about how psychosis-like experiences independently affect perceived public stigma in the non-clinical population. The aim of the present study was to examine the relationship between psychosis-like experiences and perceived public stigma in a non-clinical sample.MethodsFor this cross-sectional study, we recruited 524 individuals (239 male, 285 female) who had no lifetime history of psychiatric disorder. Participants completed questionnaires that asked for sociodemographic and clinical information, a measure of perceived public stigma (Perceived Psychiatric Stigma Scale [PPSS]), and two measures of psychosis-like experiences (Peters et al. Delusions Inventory [PDI]; Cardiff Anomalous Perceptions Scale [CAPS]).ResultsOf the sociodemographic characteristics analyzed in this study—gender, age, education level, marital status, and religion—only age simultaneously influenced PPSS, PDI, and CAPS scores. As hypothesized, perceived public stigma was positively correlated with measures of psychosis-like experiences, even after controlling for age. Furthermore, the perceived stigma was more strongly associated with delusion proneness than with anomalous perceptual experiences.ConclusionThe association between psychopathology and perceived public stigma appears to extend beyond clinically defined psychosis to more common psychosis-like experiences in a sample drawn from the general Han Chinese population.

Low-dose memantine attenuated methadone dose in opioid-dependent patients: a 12-week double-blind randomized controlled trial

Low-dose memantine might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. We investigated whether add-on memantine reduced cytokine levels and benefitted patients with opioid dependence undergoing methadone maintenance therapy (MMT) in a randomized, double-blind, controlled 12-week study. Patients were randomly assigned to a group: Memantine (5u2009mg/day) (nu2009=u200953) or Placebo (nu2009=u200975). The methadone dose required and retention in treatment were monitored. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-8, transforming growth factor (TGF)-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. General linear mixed models were used to examine therapeutic effect. After 12 weeks, Memantine-group required a somewhat lower methadone dose than did Placebo-group (Pu2009=u20090.039). They also had significantly lower plasma TNF-α and significantly higher TGF-β1 levels. We provide evidence of the benefit of add-on memantine in opioid dependent patients undergoing MMT.

Is schizophrenia associated with an increased risk of chronic kidney disease? A nationwide matched-cohort study

Objective The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD. Design A nationwide matched cohort study. Setting Taiwans National Health Insurance Research Database. Participants A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1:3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes. Primary and secondary outcome measures After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date. Results Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR=1.36, 95% CI 1.13 to 1.63; p<0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and non-steroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p<0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia. Conclusions The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period.