Effects of stimulus parameters on motor seizure duration in electroconvulsive therapy.

OBJECTIVE: This study examined the effect of stimulus parameters on the occurrence of adequate seizures and reconsidered the factors related to motor seizure duration. METHODS: The medical records of 187 patients who received ECT in Asan Medical Center from January 2007 to May 2014 were retrospectively reviewed. The starting stimulus dose was determined using a preselected-dose method and the cutoff value to determine the adequate motor seizure duration was 20-25 seconds. The association between seizure parameters and the occurrence of adequate seizure was assessed with logistic regression using a generalized estimating equation. RESULTS: Age (P<0.001), use of mood stabilizers (P=0.002), and benzodiazepine (P<0.001) were significantly lower in sessions with an adequate seizure duration but use of antidepressants (P<0.001) and clozapine (P=0.025) were significantly higher in sessions with an adequate seizure duration. In the generalized estimating equation analyses, after adjustment for age, benzodiazepine dose, and lamotrigine use, charge (odds ratio [OR] =0.999; 95% confidence interval [CI], 0.998-1.000; P=0.005), and train duration (OR =0.632; 95% CI, 0.490-0.817; P<0.001) were significantly associated with the occurrence of adequate seizure. DISCUSSION: Stimulus charge and train duration are significantly associated with motor seizure duration. However, train duration appears to have a greater effect on motor seizure duration. Additionally, age, benzodiazepine dose, and lamotrigine use independently affect motor seizure duration.

Increased diffusivity in gray matter in recent onset schizophrenia is associated with clinical symptoms and social cognition.

INTRODUCTION: Diffusion weighted MRI (dMRI) is a method sensitive to pathological changes affecting tissue microstructure. Most dMRI studies in schizophrenia, however, have focused solely on white matter. There is a possibility, however, that subtle changes in diffusivity exist in gray matter (GM). Accordingly, we investigated diffusivity in GM in patients with recent onset schizophrenia. METHODS: We enrolled 45 patients and 21 age and sex-matched healthy controls. All subjects were evaluated using the short form of the Wechsler Adult Intelligence Scale, the Positive and Negative Syndrome Scale (PANSS), and the video based social cognition scale. DMRI and T1W images were acquired on a 3 Tesla magnet, and mean Fractional Anisotropy (FA), Trace (TR) and volume were calculated for each of the 68 cortical GM Regions of Interest parcellated using FreeSurfer. RESULTS: There was no significant difference of FA and GM volume between groups after Bonferroni correction. For the dMRI measures, however, patients evinced increased TR in the left bank of the superior temporal sulcus, the right inferior parietal, the right inferior temporal, and the right middle temporal gyri. In addition, higher TR in the right middle temporal gyrus and the right inferior temporal gyrus, respectively, was associated with decreased social function and higher PANSS score in patients with schizophrenia. CONCLUSION: This study demonstrates high sensitivity of dMRI to subtle pathology in GM in recent onset schizophrenia, as well as an association between increased diffusivity in temporal GM regions and abnormalities in social cognition and exacerbation of psychiatric symptoms.

Efficacy, safety, and impact on hospitalizations of paliperidone palmitate in recent-onset schizophrenia.

OBJECTIVE: To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics. METHODS: In this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18-50 years) with recent-onset (≤5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50-150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods. RESULTS: A total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18 (mean [standard deviation, SD] change: -11.3 [21.38], P<0.0001, primary endpoint). Subgroup analysis revealed greater improvements among patients with worse disease severity at baseline: PANSS ≥70 versus <70 (mean [SD] change: -23.1 [24.62] vs -4.7 [15.98], P<0.0001 each). Secondary efficacy endpoints such as Clinical Global Impression of Schizophrenia (CGI-SCH), Medication Satisfaction Questionnaire (MSQ) scores showed significant improvements (P<0.0001) from baseline; 33.3% patients achieved symptom remission. In mirror analyses set (N=474), PP significantly (P<0.0001) reduced mean number of hospitalization days/person/year (12-month: 74.3 vs 19.7; 18-month: 74.3 vs 18.9) as well as percentage of patients requiring hospitalization in past 12 months (12-month: 39.7% vs 24.6%; 18-month: 39.7% vs 25%), and PP treatment increased the proportion of patients not requiring hospitalization (12-month: 60.3% vs 75.4%; 18-month: 60.3% vs 75%) from retrospective to prospective period. Adverse events (≥15%) were extrapyramidal symptoms-related (31.3%), injection-site pain (18.6%), and insomnia (15.2%). CONCLUSION: PP was efficacious and generally tolerable with significant reductions observed in both number of hospitalizations and days spent in hospital.

Age structure at diagnosis affects aggression in a psychiatric inpatient population: age structure affecting inpatient aggression.

Study of inpatient aggression in psychiatric inpatient units (PIUs), where vulnerable patients interact intensely in small groups, is hampered by a lack of systematic monitoring of aggressive events in the context of group dynamics. Our current study examines the relationship between aggression and group structure in the PIU of a general tertiary-care hospital over a 9-month period. The severity of aggression was monitored daily using the Overt Aggression Scale (OAS). Clinical data including the daily number and mean age of subpopulations with different diagnoses were acquired. Cross-correlation function and autoregressive integrated moving average modeling were used to assess the effects of various group structure parameters on the incidence of aggressive events in the PIU. The daily total OAS score correlated positively with the daily mean age of patients with schizophrenia and bipolar disorder. By contrast, the OAS total score demonstrated a negative correlation with the daily mean age of patients with major depression. The age of the patients at diagnosis is an important group structure that affects the incidence of aggression in a PIU.

A prospective, open-label study to evaluate symptomatic remission in schizophrenia with risperidone long-acting injectable in Korea.

This study was designed to investigate long-term clinical outcomes of risperidone long-acting injectable (RLAI) in patients with schizophrenia or schizoaffective disorder. An open-label, 48-week, prospective study of RLAI treatment was carried out at 63 centers in South Korea. Initial and maintenance dosage of RLAI were adjusted according to clinical judgment. Efficacy was measured by the remission rate, continuation rate, and changes in the clinical measurements such as eight items of the Positive and Negative Symptom Scale (PANSS), the Clinical Global Impression - Severity, and the Schizophrenia Quality of Life Scale. In terms of the safety, Simpson-Angus rating Scale, adverse events (AEs), and BMI were investigated. Of the 522 patients who were enrolled, 472 patients who had been assessed on the eight items of PANSS at baseline and at least once during RLAI treatment were included in the intention-to-treat (ITT) population. The per-protocol (PP) population included 184 patients (39.0%), who completed all assessments during 48 weeks of the follow-up period. Total scores of eight items of PANSS, Clinical Global Impression - Severity, and Schizophrenia Quality of Life Scale were reduced significantly from baseline to endpoint in both ITT and PP populations. The mean dose (SD) of RLAI was 33.2 (7.6) mg. In the PP population, the number of patients who scored 1-3 on eight items of PANSS were 47 (25.5%) at baseline and 144 (78.3%) at 48 weeks. According to the remission defining as scores 1-3 on eight items of PANSS sustaining of at least 6 months' duration by Andreasen, the numbers of patients who achieved remission were 45 (24.5%) at 24 weeks and 120 (65.2%) at 48 weeks. A significant decrease in the mean score of Simpson-Angus rating Scale and a significant increase in BMI over time in last observation carried forward were observed, and patients who fulfilled the remission criteria during the study showed more weight gain than those who did not. During the study period, a total of 645 AEs were noted in 233 patients (49.3%) who were included in the ITT population. Sixty-nine serious AEs in 51 patients were reported, but all of them were not directly attributable to administration of RLAI. This prospective, open-label study showed improvements in symptom and AEs and a significant increase in BMI during 48 weeks of biweekly RLAI treatment. The rate of study completion was 39.0% and the remission rate among those who completed the study was 65.2%. None of the serious AEs were directly related to the administration of RLAI.

18F-Fluorodeoxyglucose Positron-Emission Tomography Findings with Anti-N-Methyl-D-Aspartate Receptor Encephalitis that Showed Variable Degrees of Catatonia: Three Cases Report.

Catatonia is one of the main symptoms of anti-N-Methyl-D-aspartate receptor (NMDAR) encephalitis. However, it is unknown whether metabolic changes observed with (18)F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) are correlated with the severity of the catatonic symptoms and clinical course. Three patients with anti-NMDAR encephalitis showing variable degrees of catatonia were performed with FDG-PET scans during the acute and recovery phase. PET findings showed hypermetabolism in the frontotemporoparietal regions and bilateral basal ganglia in the patient with mild catatonia, but more widespread hypermetabolic regions including the thalamus and brainstem were observed in the patients with more severe catatonia. Follow-up PET scans in one patient showed mild hypermetabolism in the right basal ganglia that correlated with mild rigidity and tonic posturing in the left extremities. Extent of cerebral metabolic changes correlates with the severity of catatonia accompanied by behavioural, motor, autonomic, and breathing abnormalities in anti-NMDAR encephalitis.

Unnatural causes of death and suicide among former adolescent psychiatric patients.

PURPOSE: Compared with the general population, adolescent psychiatric patients are subject to premature death from all causes, but suicide-specific mortality rates in this population have not been carefully investigated. Therefore, we examined the high mortality due to unnatural causes, particularly suicide, using standardized mortality ratios (SMRs) relative to sex, diagnosis, and type of psychiatric service. METHODS: A total of 3,029 patients aged 10-19 years presented to the outpatient clinic of a general hospital in Seoul, Korea, or were admitted to that hospital for psychiatric disorders from January 1995 to December 2006. Unnatural causes mortality risk and suicide mortality risk in these patients were compared with those in sex- and age-matched subjects from the general Korean population. RESULTS: The SMR for unnatural causes was 4.6, and for suicide it was 7.8. Female subjects, the young, and inpatients had the highest risks for unnatural causes of death or suicide. Among the different diagnostic groups, patients with psychotic disorders, affective disorders, and personality disorders had significantly increased SMRs for unnatural causes, and those with psychotic disorders, affective disorders, and disruptive behavioral disorders had significantly increased SMRs for suicide. CONCLUSIONS: The risks of unnatural death and suicide are high in adolescent psychiatric inpatients in Korea, but not as high in adolescent outpatients. Effective preventative measures are required to reduce suicide mortality in adolescent psychiatric patients, particularly female patients admitted for general psychiatric care.

Evaluation of reliability of computerized neurobehavioral tests in Korean children.

Neurobehavioral tests are among the most efficient methods of identifying the adverse health effects of neurotoxicants. The reliability of neurobehavioral tests may be affected by racial or cultural backgrounds, but the widely used computerized neurobehavioral tests have been developed and standardized for Western children. It is thus necessary to assess the reliability of the existing computerized neurobehavioral tests for Korean children. For this reason, 254 healthy 7- to 8-year-old Korean children completed a neurobehavioral test-retest, with the test and retest held two months apart. Six neurobehavioral test items adapted from Korean Computerized Neurobehavioral Tests (KCNT) and modified to match the children's ability levels: Simple Reaction Time, Choice Reaction Time, Color Word Vigilance, Addition, Symbol Digit, and Finger Tapping Speed. The test reliability was assessed using the Pearson product-moment correlation coefficient (r) and the intraclass correlation coefficient (ICC). The ICCs ranged from 0.46 to 0.84 and were very similar to the Pearson coefficients. High reliability was detected in Symbol Digit (r=0.84, ICC=0.83), followed by the Finger Tapping Speed of the dominant hand (r=0.67, ICC=0.67) and of the non-dominant hand (r=0.65, ICC=0.65). The study findings suggest that the reliability of most computerized neurobehavioral tests is appropriate for epidemiological researches on Korean children, and that Symbol Digit and Finger Tapping Speed are more satisfactory bases for the periodic examination of neurobehavioral performance. These findings can also be useful in the future assembly of a neurobehavioral test battery, by providing more stable neurobehavioral test items for Korean children.

Safety of quetiapine fumarate extended release in the treatment of Korean patients with acute schizophrenia.

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of quetiapine fumarate extended release (XR) in the treatment of Korean subjects with acute schizophrenia. METHODS: This was an 8-week, multi-center, open-label, non-comparative study to evaluate the efficacy and safety of quetiapine fumarate XR at a daily dose of 400-800 mg. Changes in total scores on the Positive and Negative Syndrome Scale (PANSS) from baseline to week 8 were analyzed to evaluate the efficacy of quetiapine XR. Additionally, the Clinical Global Impression scale and the Montgomery-Åsberg Depression Rating Scale were administered. RESULTS: The mean change in PANSS total scores was -26.8, and the mean PANSS total score at the endpoint was significantly lower than that at baseline. The mean PANSS positive score, negative score, and general score showed statistically significant reductions at the end of the study. Statistically significant changes were also observed in Clinical Global Impression-Severity and Montgomery-Åsberg Depression Rating Scale scores. The most common treatment-related adverse events in the group receiving quetiapine XR were sedation (10.6%) and constipation (9.6%). CONCLUSIONS: In this study of Korean patients with acute schizophrenia, quetiapine XR showed clinical efficacy and relatively good tolerability.

Genetic Polymorphisms in the HTR2C and Peroxisome Proliferator-Activated Receptors Are Not Associated with Metabolic Syndrome in Patients with Schizophrenia Taking Clozapine.

OBJECTIVE: Genetic variation in the serotonin-2C receptor encoded by the HTR2C gene is one of the genetic determinants of antipsychotic-induced weight gain. Peroxisome proliferator-activated receptors are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. In this cross-sectional study, we investigated whether HTR2C-759C/T, HTR2C-697G/C, PPARα V227A, and PPARγ 161C/T genotypes were associated with metabolic syndrome (MetS) in patients with schizophrenia taking clozapine. METHODS: One hundred forty-six Korean patients using clozapine for more than one year were genotyped for the HTR2C-759C/T, HTR2C-697G/C, PPARα V227A, and PPARγ 161C/T polymorphisms, and their weight, waist circumference, blood pressure, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, and glucose were measured. We used the criteria for MetS proposed by the National Cholesterol Education Program-adapted Adult Treatment Panel III. RESULTS: The prevalence of MetS was 47.3% and was similar among men (49%) and women (42.9%). We found no significant differences between patients with and without MetS in terms of genotypes or allele frequencies. Logistic regression analyses also revealed no association between MetS and each genotype. CONCLUSION: We did not find significant associations between four polymorphisms (HTR2C-759C/T, HTR2C-697G/C, PPARα V227A, and PPARγ 161C/T) and MetS in patients with schizophrenia taking clozapine.

Dose pattern and effectiveness of paliperidone extended-release tablets in patients with schizophrenia.

OBJECTIVES: The objectives of this 12-week multicenter, open-label, noncomparative study were to evaluate the overall effectiveness of paliperidone extended release (ER), the feasibility of maintaining patients on the initial dose of 6 mg, and the relationship between dose pattern and treatment response in schizophrenic patients with inadequate responses to initial treatment in a natural setting. METHODS: All patients received 6 mg of paliperidone ER during the first 2 weeks, and subsequently, the dose was adjusted at each visit based on the patient response. We examined the response rate and the effectiveness of different dose patterns of paliperidone ER such as "early increase (dose increased to 9 mg at week 2)," "late increase (dose increased to 9 mg at week 4)," and "maintenance group." RESULTS: The response rate based on the Clinical Global Impression of Improvement or Severity response criteria was 33.6% or 61.7%, respectively. The proportion of patients who stayed with the initial dose of 6 mg was 44.5% and the response rate of these patients was 79.8%. When the treatment response to the initial dose of 6 mg is inadequate (Clinical Global Impression of Improvement ≥ 4 at week 2), an early increase in the dose seems to be more effective than maintenance or late increase of the initial dose. CONCLUSIONS: This study suggests that paliperidone ER may be an effective and well-tolerated antipsychotics in the treatment of patients with schizophrenia.

Efficacy and tolerability of aripiprazole: a 26-week switching study from oral antipsychotics.

OBJECTIVE: To determine if the maintenance effectiveness and tolerability of aripiprazole demonstrated in a 12-week study were maintained in an extension phase (up to 26 weeks). METHODS: This study was the extension of our switching study from other antipsychotics to aripiprazole in symptomatically stable patients with schizophrenia or schizoaffective disorder. All the patients were randomly assigned to the aripiprazole group or the non-aripiprazole group. The effectiveness analysis consisted of the comparison of the upper bound of the 95% confidence interval (CI) of the mean Clinical Global Impression-Improvement (CGI-I) score to 4 (no change) at the end of the study. RESULTS: At the baseline, the aripiprazole group (n=135) and the non-aripiprazole group (n=31) were comparable with respect to their mean ages, gender distribution, baseline Positive and Negative Syndrome Scale scores, and Clinical Global Impression-Severity (CGI-S) scores. The study showed that the mean CGI-I score was 2.92 (95% CI: 2.72-3.12) in the aripiprazole group and 2.81 (95% CI: 2.35-3.26) in the non-aripiprazole group at 26 weeks. In the aripiprazole group, the remission rates at 12 and 26 weeks were 74.8% and 72.6%, respectively, and 80.2% of the patients with remission at 12 weeks maintained their remission state until the end of the study. About one-fourth of the patients in the aripiprazole group reported one or more spontaneous treatment-emergent adverse events, such as insomnia, headache, and nausea. CONCLUSION: This study suggested that most clinically stable outpatients with schizophrenia maintain their remission states after being switched to aripiprazole, without serious symptom aggravation and adverse events over a course of 26 weeks.

Antipsychotic effects of quetiapine in naturalistic long term follow up study.

OBJECTIVE: This study aimed to examine the effectiveness of quetiapine and the effects of dosage relates to its effectiveness on schizophrenia and schizoaffective disorder in a naturalistic setting in Korean people. METHODS: This study was a 24-week, open-label, non-comparative, naturalistic study of quetiapine in patients diagnosed with schizophrenia and schizoaffective disorder according to DSM-IV. We stratified the patients into mild [(clinical global impression severity (CGI-S) <4 at baseline)] and severe groups (CGI-S >/=4 at baseline). We investigated the response rate, defined as clinical global impression improvement (CGI-I)

Sex-different association of DAO with schizophrenia in Koreans.

The gene encoding D-amino acid oxidase (DAO), which acts as a receptor for the schizophrenia-associated neurotransmitter, N-methyl-D-aspartate (NMDA), is regarded as a potential candidate gene for schizophrenia. However, the potential association of the DAO gene with schizophrenia has been the subject of some debate. Here, we tested three single nucleotide polymorphisms (SNPs) of DAO in a group of Korean schizophrenia patients, and found no significant association in the overall study subjects. Interestingly, however, we found gender-specific differences in allele distributions, with SNP rs2070586 appearing to act as a risk allele in female schizophrenia patients, but as a protective allele in males. Our data support the hypothesis that DAO plays a role in schizophrenia, possibly in a gender-dependent manner.

Preliminary evidence on the association between XBP1-116C/G polymorphism and response to prophylactic treatment with valproate in bipolar disorders.

The 116C/G polymorphism in the promoter region of XBP1 is known to be associated with bipolar disorders. The G allele of the XBP1-116C/G polymorphism has reduced XBP1-dependent transcription activity compared with the C allele. Valproate treatment has been known to rescue the impaired response of cells with the G allele. We investigated the hypothesis that the G allele of XBP1-116C/G has better prophylactic treatment response to valproate compared to the C allele. This study involved 51 patients with bipolar disorder who were treated with valproate for prophylactic treatment. Prophylactic treatment response to valproate was retrospectively assessed using a scale described by Grof et al. [Grof, P., Duffy, A., Cavazzoni, P., Grof, E., Garnham, J., MacDougall, M., O'Donovan, C., Alda, M., 2002. Is response to prophylactic lithium a familial trait? Journal of Clinical Psychiatry 63, 942-947.]. We found that the patients with the G allele of XBP1-116C/G showed a better prophylactic treatment response to valproate compared to the C allele. This result is in agreement with in-vitro data showing that valproate ameliorates the endoplasmic reticulum (ER)-stress response compromised by the G allele.

A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder.

The objectives of this 12-week multicenter open-label switching study were to evaluate the overall clinical efficacy, safety, and tolerability of aripiprazole in stable patients with schizophrenia or schizoaffective disorder, and to assess, in a naturalistic setting, whether such patients experience symptom worsening when switched from D2 receptor antagonists to aripiprazole (a D2 receptor partial agonist). Patients with schizophrenia or schizoaffective disorder in a symptomatically stable state were randomized to aripiprazole or standard-of-care antipsychotics. The Clinical Global Impression (CGI), Positive and Negative Syndrome Scale, and Investigator's Assessment Questionnaire were used monthly. The Udvalg for Kliniske Undersogelser side-effect rating scale scores and treatment emergent adverse events were recorded to assess the safety and tolerability of switching to aripiprazole from other antipsychotics. A total of 292 patients were randomly assigned to receive aripiprazole (N = 245) or non-aripiprazole antipsychotics (N = 47). Mean CGI-Improvement score at 12 weeks was 3.56+/-1.29 (95% confidence interval: 3.39-3.73) in the aripiprazole group, indicating that aripiprazole was effective in treating schizophrenic patients. Aripiprazole treatment resulted in improvement from baseline on all efficacy outcome measures, including Positive and Negative Syndrome Scale total, positive, negative, and general subscale, and CGI-Severity scores. In addition, after aripiprazole treatment, the remission rate was increased from 43.9% at baseline to 51.7% at 12 weeks. The proportion of patients with symptom worsening at 12 weeks was low (12.4%). Both Investigator's Assessment Questionnaire and Udvalg for Kliniske Undersogelser scores showed that there were fewer prolactin-related adverse events in the aripiprazole group than in the standard-of-care antipsychotics group (P<0.05). There were no significant between-group differences in time to failure to maintain remission and time to dropout. In the naturalistic setting, symptomatically stable outpatients with schizophrenia who were switched to aripiprazole showed clinically meaningful treatment benefits. The majority of patients was successfully switched from other antipsychotics without serious symptom exacerbation or adverse events over a course of 12 weeks.

Intramuscular olanzapine versus short-acting typical intramuscular antipsychotics: comparison of real-life effectiveness in the treatment of agitation.

OBJECTIVE: To compare the effectiveness of intramuscular (IM) olanzapine and typical IM antipsychotics in naturalistically treated acutely agitated patients with schizophrenia or acute mania. METHODS: During the acute phase, 2011 inpatients (including emergency settings) were assessed at 2, 24 and 72 h, and 7 days following initial injection and on oral antipsychotic transition. Mean change in agitation was assessed via Positive and Negative Symptom Scale-Excited Component (PANSS-EC) and Clinical Global Impressions-Severity (CGI-S) scores. Response (> or = 40% reduction in baseline PANSS-EC score) was analysed using logistic regression. RESULTS: Significantly greater decreases in PANSS-EC and CGI-S scores were observed in patients receiving IM olanzapine (n = 1294) as their first injection compared with patients receiving other IM antipsychotics (n = 717) (P<0.05; 2 h: effect size 0.1); IM haloperidol treatment (all assessments, P<0.05); and IM zuclopenthixol treatment (2 h, P<0.001). Higher response rates were observed with IM olanzapine compared with other IM antipsychotics at 24 and 72 h, and 7 days (P<0.05). IM olanzapine was associated with fewer extrapyramidal side effects compared with other assessed IM antipsychotics. CONCLUSIONS: IM olanzapine provided somewhat more effective control of acute agitation than other assessed IM antipsychotics.

Treatment response and duration of maintenance treatment with adjunctive antidepressants in bipolar depression: A retrospective chart review.

Objective. The aim of this study was to investigate the treatment response and optimal maintenance period of antidepressants to minimize the risk of switching in bipolar depression in clinical practice. Methods. In a retrospective chart review, 78 bipolar patients, treated for a depressive episode by adding antidepressant to ongoing mood-stabilizing medications and had been followed for at least 6 months were identified. We determined recovery to euthymia and/or switching into mania during the 6-month follow-up period and estimated the time from antidepressant initiation to mood change. Results. Antidepressants treatment responses were classified into four groups. In one group, depression was sustained for 6 months despite continuous antidepressant treatment (poor-response group, 10.3%). In the second, abrupt switch into mania occurred during antidepressant treatment (acute-switch group, 19.2%). In the third, the depression improved to euthymia without manic switching (good-response group, 50%). In the fourth, the depression improved to euthymia but manic switching occurred during maintenance with antidepressants (delayed-switch group, 20.5%), and the mean duration of antidepressants maintenance was 54.6±38.9 days. Conclusions. Bipolar depression has heterogeneous treatment responses to adjunctive antidepressant. Antidepressants should be discontinued within 8 weeks after improvement to euthymia to minimize the risk of manic switching.

Effectiveness and tolerability of long-acting risperidone: A 9-month open-label extension of a 12-week switching study from oral antipsychotics.

Objectives. The aim of this non-randomized, single-arm, multi-center, 9-month extension study was to evaluate the maintained efficacy and tolerability of long-acting risperidone injection when we switched to it from previous oral antipsychotics in symptomatically stable patients with schizophrenia or other psychotic disorders. Methods. A total of 98 patients who had completed a previous 12-week acute phase study were included. Efficacy and tolerability were assessed with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Extrapyramidal Symptom Rating Scale (ESRS). Results. The remission rate of 77.6% (76/98) at baseline and 57.1% (56/98) at the end of the study. Of patients who were in remission at baseline, 65.8% (50/76) maintained their remission state until the end. The symptom worsening rate was relatively low (11.1%), and there was no aggravation in mean PANSS total and subscale scores. Spontaneous treatment-emergent adverse events (TEAE) were reported by 21 (21.4%) patients, and most commonly reported adverse events were extrapyramidal symptoms (N=6, 6.1%) and insomnia (N=4, 4.1%). Extrapyramidal symptoms were significantly improved. Conclusions. Switching to long-acting risperidone injection from oral antipsychotics was a safe and well-tolerated strategy for maintaining clinical stability in symptomatically stable patients with schizophrenia.