Effectiveness of Switching to Long-acting Injectable Aripiprazole in Patients with Recent-onset and Chronic Schizophrenia

Objective@#This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients. @*Methods@#This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics−Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years’ duration of the illness. @*Results@#Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group. @*Conclusion@#High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent-onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.

Development of the Korea-Polyenvironmental Risk Score for Psychosis

Objective@#Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). @*Methods@#We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the “population proportion” (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). @*Results@#We first constructed the “K-PERS-I,” comprising five factors based on the PPS, and then the “K-PERS-II” comprising six factors based on the ERS. The instruments accurately predicted participants’ status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. @*Conclusion@#The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.

Defining Treatment Response, Remission, Relapse, and Recovery in First-Episode Psychosis: A Survey among Korean Experts

Objective@#For the proper treatment of first-episode psychosis, assessment of treatment response, remission, relapse, and recovery is important. Therefore, the present study aimed to develop operational definitions of clinical outcomes in first-episode psychosis. @*Methods@#A questionnaire was developed by a panel of experts and underwent three revisions. The final survey was presented to 150 psychiatrists who were members of the Korean Society for Schizophrenia Research. Respondents selected factors that they believed were important to consider while defining treatment response, remission, relapse, and recovery using a 6-point Likert scale. Selected factors that constituted each definition were statistically extracted, and operational definitions were developed. @*Results@#A total of 91 experts responded to the survey. The extent of reduction in psychopathology, socio-occupational functioning, and duration of each state were the core factors of each definition. Outcomes obtained from discussions and consultations by experts have been summarized and proposed. @*Conclusion@#The criteria developed in this survey tended to be somewhat stricter than those used by other studies. The fundamental reason for this is that this survey focused on first-episode psychosis. A better understanding of each definition in first-episode psychosis is necessary to improve effective treatment outcomes.

Switching Antipsychotics to Blonanserin in Patients with Schizophrenia: An Open-label, Prospective, Multicenter Study

OBJECTIVE: This study was performed to investigate the efficacy and tolerability of blonanserin in schizophrenic patients who were previously treated with other antipsychotics but, due to insufficient response, were switched to blonanserin. METHODS: A total of 52 patients with schizophrenia who were unresponsive to treatment with antipsychotic monotherapy or combination therapy were recruited into this 12-week, open-label, prospective, multicenter study. Patients were switched to blonanserin from their existing antipsychotics over a maximum 2-week tapering-off period. Efficacy was primarily evaluated using the 18-item Brief Psychiatric Rating Scale (BPRS). Assessments were performed at baseline, and at weeks 1, 2, 4, 8, and 12. RESULTS: Switching to blonanserin resulted in a significant decrease in the mean total score on the BPRS from baseline (56.8 ± 9.4) to week 12 (42.1 ± 13.8, p < 0.001). The most common adverse events were extrapyramidal symptoms (n = 12, 23.1%), insomnia (n = 10, 19.2%), and emotional arousal (n = 6, 11.5%). Overweight or obese patients (body mass index ≥ 23 kg/m2, n = 33) who switched to blonanserin exhibited significant weight loss from 75.2 ± 9.3 kg at baseline to 73.5 ± 9.2 kg at week 12 (p = 0.006). The total cholesterol (baseline, 236.1 ± 47.6 mg/dl; endpoint [week 12], 209.9 ± 28.0 mg/dl; p = 0.005) and prolactin levels (baseline, 80.0 ± 85.2 ng/ml; endpoint [week 12], 63.2 ± 88.9 ng/ml; p = 0.003) were also significantly improved in patients with hypercholesterolemia or hyperprolactinemia. CONCLUSION: The results of the present study suggest that switching to blonanserin may be an effective strategy for schizophrenic patients unresponsive to other antipsychotic treatments.

Avoidant Insecure Attachment as a Predictive Factor for Psychological Distress in Patients with Early Breast Cancer: A Preliminary 1-Year Follow-Up Study

OBJECTIVE: To identify attachment insecurity as an associative factor with unresolved psychological distress 1 year after surgery in the early breast cancer (BC) population. METHODS: One-hundred fourteen participants completed the Hospital Anxiety and Depression Scale (HADS) and the Experiences in Close Relationship (ECR-M36) questionnaire within 1 week (baseline) and at 1-year post-surgery (follow-up). Participants were categorized into the distress and the non-distress groups based on a HADS-total score cut-off of 15. Logistic regression analysis revealed predictive factors of distress at follow-up. RESULTS: At baseline, 53 (46.5%) participants were found to be in the distress group. The degree of distress decreased over 1 year (p= 0.003); however, 43 (37.7%) showed significant remaining distress at follow-up. Baseline scores of the ECR-M36 avoidance [odds ratio (OR)=1.045, 95% confidence interval (CI)=1.002–1.090] and HADS-total (OR=1.138, 95% CI=1.043–1.241) were predictors of distress at follow-up. CONCLUSION: A substantial proportion of early BC patients suffer distress even one-year after surgery. Avoidant attachment appeared to be an influential factor on distress in early BC patients. Moreover, the finding that initial distress level could predict one at 1-year post-operation warrant a screening and management of distress along with BC treatment.

Comparative Efficacy and Safety of Long-acting Injectable and Oral Second-generation Antipsychotics for the Treatment of Schizophrenia: A Systematic Review and Meta-analysis

We aimed to compare the efficacy and safety of long-acting injectable (LAI) and oral second-generation antipsychotics (SGAs) in treating schizophrenia by performing a systematic review and meta-analysis. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library, as well as five Korean databases, were systemically searched to identify studies published from 2000 to 16 April 2015, which compared the efficacy and safety of LAI and oral SGAs. Using data from randomized controlled trials (RCTs), meta-analyses were conducted. In addition, the GRADE (the Grading of Recommendations, Assessment, Development and Evaluation) approach was applied to explicitly assess the quality of the evidence. A total of 30 studies including 17 RCTs and 13 observational studies were selected. The group treated with LAI SGAs was characterized by significantly lower relapse rates, longer times to relapse and fewer hospital days, but also by a higher occurrence of extrapyramidal syndrome and prolactin-related symptoms than that in the group treated with oral SGAs. Our findings demonstrate that there is moderate to high level of evidence suggesting that in the treatment of schizophrenia, LAI SGAs have higher efficacy and are associated with higher rates of extrapyramidal syndrome and prolactin-related symptoms. Additionally, the use of LAI SGAs should be combined with appropriate measures to reduce dopamine D2 antagonism-related symptoms.

Posttraumatic Embitterment Disorder and Hwa-byung in the General Korean Population

OBJECTIVE: Posttraumatic embitterment disorder (PTED) is characterized by states of “embitterment”, characteristically similar to “Hwa-byung”, which is a Korean culture-bound syndrome. The present study aimed to assess diagnostic relationships between PTED and Hwa-byung. METHODS: A total of 290 participants completed our survey. PTED and Hwa-byung were diagnosed using a diagnostic interview and scale. Scales for depression, suicide ideation, and anger were used for evaluation. Fisher's exact tests and Mann-Whitney U tests were performed to evaluate diagnostic overlap between PTED and Hwa-byung, and associations of scale scores for depression, suicide ideation, and anger between the PTED, Hwa-byung, and non-diagnosed groups. Associations of these scales between the depressive and non-depressive groups, and suicidal and non-suicidal groups were also evaluated. RESULTS: Among the participants, 1.7% of the sample fit the diagnostic criteria for PTED and 2.1% fit the criteria for Hwa-byung. No individual fit the criteria for both. Anger scores were significantly higher in the Hwa-byung group than in the non-diagnostic group. There were not any significant differences in anger scores between the PTED and non-diagnostic groups. Depression scores were significantly higher in the PTED than in the non-diagnostic groups. In contrast, no significant differences were observed between depression scores in the Hwa-byung and non-diagnostic groups. CONCLUSION: These results suggest that PTED may be a disorder category that is distinct from Hwa-byung.

Design and Methodology of the Korean Early Psychosis Cohort Study

The present study details the rationale and methodology of the Korean Early Psychosis Cohort Study (KEPS), which is a clinical cohort investigation of first episode psychosis patients from a Korean population. The KEPS is a prospective naturalistic observational cohort study that follows the participants for at least 2 years. This study includes patients between 18 and 45 years of age who fulfill the criteria for one of schizophrenia spectrum and other psychotic disorders according to the diagnostic criteria of DSM-5. Early psychosis is defined as first episode patients who received antipsychotic treatment for fewer than 4 consecutive weeks after the onset of illness or stabilized patients in the early stages of the disorder whose duration of illness was less than 2 years from the initiation of antipsychotic treatment. The primary outcome measures are treatment response, remission, recovery, and relapse. Additionally, several laboratory tests are conducted and a variety of objective and subjective psychiatric measures assessing early life trauma, lifestyle pattern, and social and cognitive functioning are administered. This long-term prospective cohort study may contribute to the development of early intervention strategies and the improvement of long-term outcomes in patients with schizophrenia.

Reliability and Validity of the Korean Young Schema Questionnaire-Short Form-3 in Medical Students

OBJECTIVE: The Young Schema Questionnaire (YSQ) is a self-report measure of early maladaptive schemas and is currently in its third revision; it is available in both long (YSQ-L3) and short (YSQ-S3) forms. The goal of this study was to develop a Korean version of the YSQ-S3 and establish its psychometric properties in a Korean sample. METHODS: A total of 542 graduate medical students completed the Korean version of the YSQ-S3 and several other psychological scales. A subsample of 308 subjects completed the Korean YSQ-S3 both before and after a 2-year test-retest interval. Correlation, regression, and confirmatory factor analyses were performed on the data. RESULTS: The internal consistency of the 90-item Korean YSQ-S3 was 0.97 and that of each schema was acceptable, with Cronbach's alphas ranging from 0.59 to 0.90. The test-retest reliability ranged from 0.46 to 0.65. Every schema showed robust positive correlations with most psychological measures. The confirmatory factor analysis for the 18-factor structure originally proposed by Young, Klosko, and Weishaar (2003) showed that most goodness-of-fit statistics were indicative of a satisfactory fit. CONCLUSION: These findings support the reliability and validity of the Korean version of the YSQ-S3.

The Role of Childhood Trauma on Early Maladaptive Schema Domain / 신경정신의학

OBJECTIVES: The aim of this study was to investigate the effect of childhood trauma on early maladaptive schema domains. METHODS: A total of 305 graduate students completed the Young Schema Questionnaire-Short Form, the Korean version of the Childhood Trauma Questionnaire (K-CTQ), and the Beck Depression Inventory. RESULTS: According to the classification based on the total score of the K-CTQ, the group that experienced childhood trauma (n=41) showed higher scores than the group with no trauma (n=264) in all five schema domains. Subsequent multiple regression analyses revealed that four out of five schema domains were significantly explained by childhood trauma ; among them, childhood trauma was the most significant predictor of the Disconnection and Rejection schema domain, accounting for 15% of the total variance in this domain (F=8.1, p<0.001). In terms of the types of childhood trauma, emotional neglect had significant general effects on all schema domains except the Impaired Limits domain. CONCLUSION: These findings in a nonclinical sample support the notion that childhood traumatic experiences may significantly impact the maladaptive schema domains, particularly the Disconnection and Rejection schema domain. In addition, this study emphasized the diffuse impact of emotional neglect upon schema domains, which may be overlooked because of its implicit nature.

Differences between Physostigmine- and Yohimbine-induced States Are Visualized in Canonical Space Constructed from EEG during Natural Sleep-wake Cycle in Rats

Although quantitative EEG parameters, such as spectral band powers, are sensitive to centrally acting drugs in dose- and time-related manners, changes of the EEG parameters are redundant. It is desirable to reduce multiple EEG parameters to a few components that can be manageable in a real space as well as be considered as parameters representing drug effects. We calculated factor loadings from normalized values of eight relative band powers (powers of 0.5, 1.0~2.0, 2.5~4.0, 4.5~5.5, 6.0~8.0, 8.5~12.0, 12.5~24.5, and 25~49.5 Hz bands expressed as ratios of the power of 0.5-49.5 Hz band) of EEG during pre-drug periods (11:00~12:00) by factor analysis and constructed a two-dimensional canonical space (reference canonical space) by canonical correlation analysis. Eight relative band powers of EEG produced by either physostigmine or yohimbine were reduced to two canonical scores in the reference canonical space. While changes of the band powers produced by physostigmine and yohimbine were too redundant to describe the difference between two drugs, locations of two drugs in the reference canonical space represented the difference between two drug's effects on EEG. Because the distance between two locations in the canonical space (Mahalanobis distance) indicates the magnitude of difference between two different sets of EEG parameters statistically, the canonical scores and the distance may be used to quantitatively and qualitatively describe the dose-dependent and time-dependent effects and also tell similarity and dissimilarity among effects. Then, the combination of power spectral analysis and statistical analysis may help to classify actions of centrally acting drugs.

Prevalence and Correlates of Major Mental Disorders among Korean Adults : A 2006 National Epidemiologic Survey / 신경정신의학

OBJECTIVES : The aims of this study are to estimate the prevalence of the DSM-IV psychiatric disorders in the Korean population using the Korean version of Composite International Diagnostic Interview (K-CIDI), and to compare those with previous studies. METHODS : The Korean Epidemiologic Catchment Area study Replication (KECA-R) was conducted between August 2006 and April 2007. The sampling of the subjects was carried out across 12 catchment areas. A multistage, cluster sampling design was adopted. The target population included all eligible residents aged 18 to 64 years. Face-to-face interviews were conducted with the Korean version of Composite International Diagnostic Interview (K-CIDI) based on the DSM-IV (N=6,510, response rate=81.7%). RESULTS : A total of 6,510 participants completed the interview. The lifetime and 12-month prevalence rates for all types of DSM-IV disorders were 30.0% and 17.3%, respectively. Those of specific disorders were as follows : 1) alcohol use disorder, 16.2% and 5.6% ; 2) nictotine use disorder, 9.0% and 6.0%;3) specific phobia, 3.8% and 3.4%;4) major depressive disorder, 5.6% and 2.5% ; and 5) generalized anxiety disorder, 1.6% and 0.8%. Data relating to nicotine and alcohol use disorder revealed a very high male/female ratio. Mood disorder and anxiety disorder were more prevalent among females than males. CONCLUSION : The prevalence of psychiatric disorders was high. In comparison with other studies, remarkable differences in the distribution of psychiatric disorders across the country and times were observed.

The Subjective Effect of Quetiapine Monotherapy on Sleep and Daytime Sleepiness in Acute Manic Patient / 대한정신약물학회지

OBJECTIVE: It is well known that treatment with quetiapine can easily cause somnolence and daytime sleepiness in patients with bipolar disorder. Such sedation may be the discomfort to the drug in terms of patient's perspectives and results in drug noncompliance. This study was aimed to investigate the effect of 6-week quetiapine monotherapy on subjective aspects of sleep in patients with acute bipolar disorder. METHODS: In a Korean multi-center, open-label, 6-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic or mixed episodes) were included to treatment with quetiapine. The dose of quetiapine initially started at 200 mg/day and rapid titrated up to 800 mg/day within day 7 according to the clinical judgements. Clinical improvement was evaluated using Young Mania Rating Scale (YMRS) and Clinical Global Impression-Bipolar version (CGI-BP). Extrapyramidal side effects were measured by Simpson-Angus Rating Scale (SARS) and Barnes Akathisia Rating Scale (BARS). The overall subjectively reported adverse events were gathered during the study period. Subjective sleep questionnaire modified from Leeds Sleep Evaluation Questionnaire (LSEQ) was used to assess the subjective measures of sleep, which included the aspects covering the ease of getting to sleep (GTS), quality of sleep (QOS) and hangover behavior next day (HOV). All assessments were done at baseline and days 7, 14, 21 and 42 after treatment with quetiapine. Analyses were focused to compare the differences between pre-drug baseline and post-treatment with quetiapine. RESULTS: Total 78 (male=30, female=48) patients were included and most of them were inpatients (N=59, 74.7%). Fifty-nine (75.9%) patients were completed the study. Mean changes of YMRS from baseline were significant at days 7, 14, 21 and 42. There were no significant differences from baseline in SARS and BARS at any assessment points. The common subjectively reported adverse events were somnolence, dizziness and dry mouth. While mean changes of 5 items measuring nighttime sleep (GTS and QOS) from baseline were significantly improved at days 7, 14, 21 and 42, those of HOV were not differed between baseline and post-treatment assessments. CONCLUSION: Data showed that quetiapine monotherapy had favorable effect on acute manic symptoms and well tolerated. Also this result suggests that quetiapine monotherapy may improve the self-perceived quality of sleep without any daytime impairment following sleep in acute manic patients.

The Efficacy and Safety of Quetiapine Monotherapy in Patients with Acute Mania: A Multi-Center, Open-Label Trial / 대한정신약물학회지

OBJECTIVE: Recently, the atypical antipsychotics such as quetiapine, olanzapine, risperidone, aripiprazole and ziprasidone are increasingly used in the management of acute manic patients as the monotherapy. But there are only a few reports on the use of these drugs in the treatment of bipolar disorder in Korea. The aim of this study was to evaluate the efficacy and tolerability of quetiapine monotherapy in patients with acute mania. METHOD: This study is multi-center, open-label, 6-week evaluation of the efficacy of quetiapine in bipolar mania. In this study, patients with a DSM-IV diagnosis of bipolar I disorder (manic or mixed episodes) were included to treatment with quetiapine (flexibly dosed up to 800 mg/day). Clinical improvements were rated by Young Mania Rating Scale (YMRS), Clinical Global Impression-Bipolar Version (CGI-BP), Brief Psychiatric Rating Scale (BPRS) and Montgomery-Asberg Depression Rating Scale (MADRS). Adverse events were measured using Simpson-Angus Rating Scale (SARS) and Barnes Akathisia Rating Scale (BARS), and subjective reports of patients were evaluated. Global Assessment Scale (GAS) was used to evaluate the general functioning of patients. All assessments were done at baseline and at days 7, 14, 21, and 42 except GAS (at days 21 and 42). Analyses were focused on change from baseline to day 42. RESULTS: Total 78 (male=30, female=48) patients were included and 59 patients (75.6%) completed the study. The mean initial dose of quetiapine was 268.0+/-223.2 mg/day and mean daily dose at day 42 was 585.3+/-244.5 mg/day. YMRS and CGI-BP were significantly improved at day 7, 14, 21, and 42 as compared to baseline. Mean scores of BPRS and MADRS were also significantly decreased at the each assessment points. Fifty-two patients (66.7%) showed response (more than 50% of decrease in YMRS score from baseline) and 35 patients (44.6%) reached remission (YMRS score < or =12) at day 21. GAS showed the improvements of patient's global functioning at days 21 and 42 of quetiapine monotherapy compared to baseline. There was no significant difference between baseline and any assessment points on SARS and BARS scores. CONCLUSIONS: The data showed that quetiapine monotherapy has favorable effects across a broad range of mood symptoms with minimal adverse events in addition to functional improvement in acute manic patients. This result suggests that quetiapine may be preferred for patients with acute mania as one of the first-line agents.

A Reliability and Validity Study of the Reciprocal Attachment Questionnaire: Korean Version (RAQ-K)(I) / 신경정신의학

OBJECTIVES: The aim of this study was to develop the Reciprocal Attachment Questionnaire-Korean version (RAQ-K). METHODS: The authors tested the reliability of dimensional and pattern scales of RAQ-K with Crohnbach's alpha, test-retest reliability and interscale correlation, and construct validity with factor analysis. The subjects were Korean undergraduate students: 234 males and 249 females in the medical and nursing schools of Kyungpook National University. RESULTS: The dimensional scale of RAQ-K proved to be reliable in terms of Crohnbach's alpha coefficient except Availability and Use subscales, test-retest reliability and interscale correlation. The pattern scales of RAQ-K were reliable. Both dimensional and pattern scales were valid with two factor orthogonal rotation. CONCLUSION: The authors found RAQ-K retained available psychometric properties. But further study with some consideration to develop RAQ-K is expected. This research should assess samples of various age groups or various kinds of patients after considering two subscales. The authors stress that it is very important to consider the cultural difference between the East and the West and characteristics of Korean culture in developing a Korean version of foreign scales.