Cholinesterase inhibitors for Alzheimer disease: do they provide more than symptomatic benefits?

OBJECTIVE: This study aims to examine survival of patients with Alzheimer disease (AD) receiving clinical efficacy of cholinesterase inhibitors (ChEIs) and to compare their survival with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. DESIGN, SETTING, AND PARTICIPANTS: The retrospective cohort study used national mortality data provided by the Korean National Statistics Office and electronic database of 15 general hospitals on older patients who began outpatient treatment with psychiatric medications including ChEIs (N = 3,813). The authors controlled for confounding by using multivariate models and propensity scoring methods. MEASUREMENTS: Mortality rate of patients with AD receiving ChEIs was compared with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. RESULTS: Observed additional survival of patients with AD receiving ChEIs (mortality rate: 13.1%), when compared with patients with AD who never received ChEIs (15.4%) was not statistically significant (p = 0.74; hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 0.67-1.59). Patients with AD receiving ChEIs showed higher mortality rate (13.1%) compared with that of cognitively intact old psychiatric outpatients (8.6%) (p <0.001; HR: 1.60, 95% CI: 0.96-2.68). CONCLUSION: This study does not support that ChEIs increase survival of patients with AD, compared with patients with AD who have never treated with ChEIs. Therefore, all ChEIs should be considered for symptomatic use only and not to be capable of modifying mortality of patients with AD.

Stabilization of the internal structure of persistent auditory verbal hallucinations in schizophrenia.

OBJECTIVE: Numerous studies have been conducted to investigate the phenomenological characteristics of auditory verbal hallucinations in schizophrenia. Difficulties in understanding the clinical significance of auditory verbal hallucinations may be attributed to the changes in symptom structure over the long-term course of the illness. The purpose of the present study was therefore to investigate the longitudinal changes in the phenomenological dimensions of auditory verbal hallucinations in patients with schizophrenia. METHODS: Using the Psychotic Symptom Rating Scales-Auditory Hallucination Subscale, 40 patients meeting DSM-IV criteria for schizophrenia (drug-naive first-episode schizophrenia, n=21; and drug-free chronic schizophrenia, n=19) who reported persistent auditory verbal hallucinations were assessed before the initiation of antipsychotic treatment and after 6 months of treatment. To detect the changes in underlying clusters of phenomenological variables, hierarchical clustering and multidimensional analysis were performed. RESULTS: The phenomenological variables of auditory verbal hallucinations formed two main clusters with 6 month treatment: emotional and cognitive. Physical characteristics failed to indicate a stable cluster. Psychosocial disruption, which initially formed a cluster with cognitive variables, congregated with emotional variables at 6 months. Subgroup analysis indicated that the cluster structure of the first-episode group showed more dynamic changes than did that of the chronic schizophrenia group. CONCLUSIONS: Phenomenological variables characterizing persistent auditory verbal hallucinations can be differentiated into emotional and cognitive clusters with achievement of symptom stabilization, and the changes in physical characteristics may not be the sole sign of clinical improvement.

The Impact of Paliperidone Palmitate on Hospitalization in Patients with Schizophrenia: A Retrospective Mirror-image Study.

OBJECTIVE: Whether long-acting injectable antipsychotics (LAI) are superior to oral antipsychotics remains a controversial question, and results vary depending on the study design. Our study was performed to compare outcomes of oral antipsychotics and paliperidone palmitate (PP) in clinical practice by investigating the numbers of admissions and bed days. METHODS: We performed a retrospective observational mirror-image study at a single medical center, reviewing medical charts to obtain the clinical data. Forty-six patients with a diagnosis of schizophrenia or schizoaffective disorder who had received at least two doses of PP were included in the analysis. The Wilcoxon signed-rank test was used to compare the numbers of bed days and admissions 1 year before starting PP with those numbers at 1 year after. RESULTS: The mean number of admissions fell from 0.83 to 0.17 per patient (p < 0.0002), and the median fell from 1 to 0. The mean number of bed days decreased significantly, from 24.85 to 8.74 days (p < 0.006). The outcomes remained similar in sensitivity analyses set up with different mirror points. CONCLUSION: Our results indicate that initiating PP reduced the mean numbers of hospital admissions and bed days compared with prior oral medication. LAIs may thus be cost effective in practice; its use bringing about cost reductions greater than its purchase cost.

Validation of the Korean Version of the Clinical Assessment Interview for Negative Symptoms.

OBJECTIVE: Clinical Assessment Interview for Negative Symptoms (CAINS) has recently been developed to improve measurement of negative symptoms in schizophrenia. We performed a multi-center study to validate the Korean version of the CAINS (CAINS-K) and explore potential cultural variation. METHODS: One hundred eighty schizophrenia patients diverse in demographic and illness profile were recruited from four centers in Korea. Along with the CAINS-K, the Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Calgary Depression Scale for Schizophrenia (CDSS), a self-report measure of behavioral inhibition and activation (BIS/BAS) and neurocognitive tasks were administered to verify external validities. RESULTS: The CAINS-K showed high internal-consistency (0.92) and inter-rater reliability (0.77). Exploratory Factor Analysis replicated a two-factor structure of the original scale including motivation/pleasure and expression deficits dimensions. Korean patients tended to report lower pleasure compared to American patients in the prior study. The CAINS-K showed an adequate convergent validity with the SANS, negative symptoms of the BPRS, and BAS. A divergent validity was supported as the CAINS-K showed zero or only weak correlations with other symptoms of the BPRS, depression from the CDSS, and neurocognitive tasks. CONCLUSION: The CAINS-K demonstrated high internal consistency and adequate external validities, and is expected to promote studies on negative symptoms in Korean patients with schizophrenia.

Prevalence of Metabolic Syndrome in Patients with Schizophrenia in Korea: A Multicenter Nationwide Cross-Sectional Study.

OBJECTIVE: We designed a nationwide study with limited exclusion criteria to investigate the prevalence of metabolic syndrome (MetS) in Korea and its relationship with antipsychotic medications. METHODS: This multicenter, cross-sectional, and observational study included patients diagnosed with schizophrenia or schizoaffective disorder. Sixteen hospitals enrolled 845 patients aged 18 to 65 years prescribed any antipsychotic medication between August 2011 and August 2013. MetS was diagnosed using the criteria of the modified Adult Treatment Panel III of the National Cholesterol Education Program with the Korean abdominal obesity definition (waist circumference ≥85 cm in women, ≥90 cm in men). RESULTS: The prevalence of MetS in all patients was 36.5% and was significantly higher in men than women (men, 40.8%; women, 32.2%) and was significantly correlated with age [odds ratio (OR) 1.02] and duration of illness (OR 1.03). The prevalence of MetS across antipsychotic drugs in the major monotherapy group was as follows: 18.8% for quetiapine, 22.0% for aripiprazole, 33.3% for both amisulpride and paliperidone, 34.0% for olanzapine, 35% for risperidone, 39.4% for haloperidol, and 44.7% for clozapine. CONCLUSION: The prevalence of MetS is very high in patients with schizophrenia or schizoaffective disorder. Screening and monitoring of MetS is also strongly recommended.

Measuring negative symptoms in patients with schizophrenia: reliability and validity of the Korean version of the Motivation and Pleasure Scale-Self-Report.

BACKGROUND: The Clinical Assessment Interview for Negative Symptoms (CAINS) is one of the validated interview measures of negative symptoms in psychotic disorders. The Motivation and Pleasure Scale-Self-Report (MPSR) is a self-report measure that assesses the motivation and pleasure domains of negative symptoms based on the CAINS. This study evaluated the reliability and validity of a Korean version of the MPSR. METHODS: A total of 139 patients with schizophrenia completed the MPSR, CAINS, Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scales, Calgary Depression Scale for Schizophrenia, and other measures of trait and cognitive function. RESULTS: The 15-item MPSR showed good internal consistency. In addition, it also had a good convergent validity with the Motivation and Pleasure subscale of the CAINS and the anhedonia/avolition subscale of the SANS. The scale was not associated with psychotic symptoms, agitation/mania, and depression/anxiety, and it showed good discriminant validity. MPSR scores were significantly correlated with Behavioral Activation System total score for trait measure. CONCLUSION: The Korean version of the MPSR is a notable self-report method for examining the severity of negative symptoms in schizophrenia.

The effectiveness of cross-tapering switching to ziprasidone in patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: Switching antipsychotics is one useful therapeutic option when the treatment of schizophrenia encounters suboptimal efficacy and intolerability issues. This study aimed to investigate the efficacy and tolerability of cross-tapering switching to ziprasidone from other antipsychotics. METHODS: A total of 67 patients with schizophrenia or schizoaffective disorder were recruited in this 12-week, multicenter, non-comparative, open-label trial. Prior antipsychotics were allowed to be maintained for up to 4 weeks during the titration of ziprasidone. Efficacy was primarily measured using the 18-item Brief Psychotic Rating Scale (BPRS) at baseline, 4 weeks, 8 weeks, and 12 weeks. Efficacy was secondarily measured by the Clinical Global Impression-Severity (CGI-S) scale and the Global Assessment of Functioning (GAF) scale at each visit. Regarding the metabolic effects of switching to ziprasidone, weight, body mass index (BMI), waist-to-hip ratio (WHR), and lipid profile-including triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol levels-were measured at each follow-up visit. RESULTS: The BPRS scores were significantly improved at 12 weeks after switching to ziprasidone (F=5.96, df=2.11, p=0.003), whereas the CGI-S and GAF scores were not significantly changed. BMIs, WHRs, and TG levels were significantly decreased, with no significant changes in other lipid profiles. CONCLUSION: Cross-tapering switching to ziprasidone is effective for patients with schizophrenia spectrum disorders. Beyond the efficacy of the procedure, favorable metabolic profiles show that switching to ziprasidone may be helpful for maintenance therapy over an extended period.

Decreased connectivity of the default mode network in pathological gambling: a resting state functional MRI study.

The default mode network (DMN) represents neuronal activity that is intrinsically generated during a resting state. The present study used resting-state fMRI to investigate whether functional connectivity is altered in pathological gambling (PG). Fifteen drug-naive male patients with PG and 15 age-matched male control subjects participated in the present study. The pathological gambling modification of the Yale-Brown Obsessive Compulsive Scale (PG-YBOCS), the Beck Depression Inventory, and the Beck Anxiety Inventory were used to determine symptom severity in all participants. Participants were instructed to keep their eyes closed and not to focus on any particular thoughts during the 4.68-min resting-state functional scan. The patients with PG displayed decreased default mode connectivity in the left superior frontal gyrus, right middle temporal gyrus, and precuneus compared with healthy controls. The severity of PG symptoms in patients with PG was negatively associated with connectivity between the posterior cingulate cortex seed region and the precuneus (r=-0.599, p=0.018). Decreased functional connectivity within DMN suggests that PG may share similar neurobiological abnormalities with other addictive disorders. Moreover, the severity of PG symptoms was correlated with decreased connectivity in the precuneus, which may be important in the response to treatment in patients with PG.

Association between Alcoholism Family History and Alcohol Screening Scores among Alcohol-dependent Patients.

OBJECTIVE: Several tests can be used to screen for alcohol dependence (AD), a prevalent disease with a heterogeneous etiology. As some patients with AD have a strong familial tendency in this regard, a family history of alcohol use disorders can affect the outcomes of screening tests and diagnostic evaluations for AD. In this study, we evaluated associations between a family history of alcohol use disorders and evaluations using the Cut down, Annoyed, Guilty, Eye-opener (CAGE) test, Alcohol Use Disorder Identification Test (AUDIT), and Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) diagnostic criteria among patients with AD. METHODS: We recruited 487 male patients with AD from eight hospitals in Korea. Patients were evaluated using the CAGE, AUDIT, and DSM-IV diagnostic criteria. Patients with and without family histories were compared in terms of these assessment tools. RESULTS: Drinking initiation, uncontrollable drinking, and problem drinking occurred earlier and CAGE "annoyed" scores were higher in patients with a family history. Alcohol problems before the age of 25 years, frequency of spontaneous or compulsive alcohol-seeking behavior, and frequencies of psychological dependence and guilt related to alcohol use were also higher. CONCLUSION: Earlier drinking problems, higher scores on specific items of the CAGE, and AUDIT, and meeting more diagnostic criteria indicate more dependent, harmful drinking by patients with AD who have a family history of this condition. Clinicians should consider patients' family history of alcohol use disorders when screening for AD to identify the correct diagnosis and develop appropriate treatment plans for these patients.

Psychometric properties of Peters et al. delusions inventory-21 in adolescence.

We explored the psychometric properties of the Korean version of the Peters et al. delusions inventory-21 (PDI-21) and evaluated the item characteristics of the PDI-21 compared with the Magical Ideation Scale (MIS) in Korean community adolescents. Survey participants comprised 310 Year 10 students who were assessed with the following instruments: the PDI-21, the MIS, the Schizotypal Personality Scale (STA) and the symptom checklist-90-R (SCL-90-R). The item characteristics of the PDI-21 and MIS were also explored using item response theory (IRT). The PDI-21 exhibited good internal consistency and demonstrated significant correlations with the MIS, STA and all subscale scores of the SCL-90-R, indicating psychological distress in adolescents with high PDI-21 scores. We also found through IRT analysis that the PDI-21 provides more information at the lower range and the MIS at the higher range of delusion proneness. Our findings suggest that the PDI-21 is an effective and reliable self-report measure for assessment of delusion proneness and that the PDI-21 and the MIS may be used complementarily to assess a broad range of delusion proneness among community adolescents.

Clinician-rated functioning and patient-rated quality of life in schizophrenia: implications of their correspondence for psychopathology and side effects.

OBJECTIVE: Past studies have found inconsistent associations between subjective and objective measures of quality of life (QOL) in schizophrenia. We hypothesized that this may be due to heterogeneity in the demographic and/or clinical variables inherent in the samples and we investigated this possibility. METHODS: We stratified the patients according to a descriptive measure of correspondence between self-reported QOL and clinician-rated functioning. We then examined whether heterogeneous patterns existed among the subgroups in terms of demographic variables, symptom severity, associations between self-reported and clinician-rated psychopathology and associations between side effects, QOL and functioning. RESULTS: The subgroups significantly differed with respect to clinician-rated positive symptoms (F=3.075, p<.05), subjective symptoms (somatization, F=5.768, p<.01; obsessive-compulsive, F=3.885, p<.05; interpersonal sensitivity, F=8.278, p<.001; depression, F=9.368, p<.001; anxiety, F=6.909, p<.01; hostility, F=7.787, p<.01; phobic anxiety, F=9.551, p<.001; paranoia, F=5.304, p<.01; psychoticism, F=5.071, p<.01) and in- and outpatient ratio (Chi(2)=11.58, p<.01). Only the subgroup with relatively good correspondence between clinician-rated functioning and self-reported QOL showed significant low to moderate associations between the aforementioned measures and side effects. In addition, they showed similar levels of significant associations between the positive and subjective symptoms. In contrast, other discordant subgroups lacked overall associations between side effects, functioning and QOL as well as between subjective and objective measures of psychopathology. CONCLUSION: Low to moderate levels of correspondence between subjective QOL and objective functioning were partly supportive of the independence of the constructs. Insight is likely to be a mediating variable of the correspondence between self-report and clinician-rated measures and should be considered in studies using self-report measures.

Efficacy and tolerability of Blonanserin in the patients with schizophrenia: a randomized, double-blind, risperidone-compared trial.

OBJECTIVES: The objective of this study was to evaluate the efficacy and tolerability of blonanserin for the treatment of Korean patients with schizophrenia using a double-blind risperidone-compared design. METHODS: Patients aged 18 to 65 years with schizophrenia were randomly assigned to blonanserin or risperidone treatment for 8 weeks. The efficacy was assessed using the mean change in Positive and Negative Syndrome Scale score total scores from baseline to week 8. Safety assessments included monitoring of vital signs, a physical examination, laboratory tests, and adverse events. RESULTS: Of 206 randomly enrolled patients, 103 receiving blonanserin and 103 receiving risperidone were included in the analysis. In this study, noninferiority between blonanserin and risperidone was demonstrated. The mean change in the Positive and Negative Syndrome Scale total score at the final evaluation time point was -23.48 +/- 19.73 for the blonanserin group and -25.40 +/- 18.38 for the risperidone group. Adverse events, which occurred less frequently in the blonanserin than in the risperidone group, included dysarthria (P = 0.0288), dizziness (P = 0.0139), increased alanine aminotransferase and aspartate aminotransferase (P = 0.0095 and P = 0.0032, respectively), and increased level blood prolactin (P = 0.0012). On the other hand, the adverse events that occurred more frequently in the blonanserin than in the risperidone group was hand tremor (P = 0.0006). CONCLUSIONS: Blonanserin was effective in the treatment of Korean patients with schizophrenia compared with risperidone and was more tolerable with a better safety profile, particularly with respect to prolactin elevation. These findings suggest that blonanserin is useful in the treatment of schizophrenia.

Measuring psychosis proneness in a nonclinical Korean population: is the Peters et al Delusions Inventory useful for assessing high-risk individuals?

OBJECTIVES: We examined the psychometric properties of the Korean version of the Peters et al Delusions Inventory (PDI) 40 and investigated the distribution of delusional ideation in a nonclinical population. We also used the item response theory to evaluate the usefulness of the PDI in measuring the risk for psychosis. METHODS: A total of 310 nonclinical individuals completed the Korean PDI-40, the Magical Ideation Scale (MIS), and the Schizotypal Personality Scale (STA). In addition, 60 psychotic inpatients with delusions completed the PDI-40. Among 310 individuals, 124 participated in a follow-up study 6 months after completing their original questionnaire. RESULTS: The PDI-40 revealed a slightly skewed distribution, but the score range was similar to that of the British population. Scores were negatively correlated with age, but no sex differences were found. The Korean PDI-40 exhibited good internal consistency and test-retest reliability. The PDI was significantly correlated with the MIS and the STA. Ten components were extracted through a principal component analysis with varimax rotation. The test results using item response theory revealed 39 items as the items which individuals with very high level of psychosis proneness will answer as "yes." Moreover, all items yielded "above moderate" discrimination in terms of psychosis proneness. CONCLUSIONS: We confirmed the reliability and validity of the Korean PDI-40. The usefulness of the PDI-40 in a nonclinical population was replicated in the Korean sample. The PDI-40 can be used as an informative device when investigating "psychosis proneness" in a group at high risk for psychosis.