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Aims: We examined prescription patterns in maintenance treatment for recovered bipolar patients and compared these with acute treatments., Methods: Using retrospective methods, the bipolar patients in clinical recovery (Clinical Global Impression Bipolar Version score ≤ 2 for 6 months) after acute episode were selected. We reviewed differences between prescription patterns at remission and after a maintenance period of at least 6 months., Results: A total of 340 bipolar disorder patients were selected. During the maintenance period, more than half of the patients (192, 56.5%) took a mood stabilizer (MS) + antipsychotic (AP) combination. Among the MS, valproate (149, 43.8%) was most prescribed, and lithium (98, 28.8%) was second, but as patients moved into maintenance treatment, lithium use decreased, and the use of lamotrigine (86, 25.3%) increased. Preferred AP were quetiapine (125, 36.8%), aripiprazole (67, 19.7%), risperidone (48, 14.1%), and olanzapine (39, 11.5%). The use of olanzapine in maintenance was greatly decreased compared with that during acute treatment (67, 19.7%). Most patients did not take an antidepressant (AD), but the proportion using one or more AD was increased during maintenance (17.9% to 30.3%), and bupropion (28, 8.2%) was the preferred AD. Doses were decreased in all drugs, but lamotrigine was maintained at a dose of 133.2 ± 68.5 mg/day., Conclusions: The most common prescription combination for bipolar maintenance treatment was MS + AP. The use of AP was decreased, whereas the use of AD in combination with MS and/or AP was increased. The doses of MS and AP were generally decreased during the maintenance periods, with the exception of lamotrigine., (© 2015 The Authors. Psychiatry and Clinical Neurosciences © 2015 Japanese Society of Psychiatry and Neurology.)

We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive-compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive-compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive-compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin-picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair-pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive-compulsive and related disorders., (© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.)

Aim: We compared the 1-year rehospitalization rates of first-episode bipolar manic patients who were discharged while being treated with lithium or valproate in combination with an atypical antipsychotic., Methods: We investigated the rehospitalization status of first-episode bipolar manic patients who were discharged between 1 January 2003 and 31 December 2010 while they were taking lithium or valproate in combination with aripiprazole, olanzapine, quetiapine, or risperidone. Rehospitalization rates during a 1-year period after discharge were compared between the group receiving lithium plus an atypical antipsychotic and the group receiving valproate plus an atypical antipsychotic using the Kaplan-Meier method. A Cox regression model was used to analyze covariates hypothesized to affect time to rehospitalization., Results: The rehospitalization rate was 17.3% during the 1-year follow-up period. We found significant differences in the rehospitalization rates of patients in the lithium (23.1%) and the valproate (13.3%) groups using the Kaplan-Meier formula. According to Cox proportional hazards regression analysis, higher Clinical Global Impression-Bipolar Version-Severity score at discharge (P = 0.005) and lithium treatment (P = 0.055) contributed to the risk of rehospitalization., Conclusion: Treatment with valproate and an atypical antipsychotic can be more effective than treatment with lithium and an atypical antipsychotic in preventing rehospitalization during the 1 year after hospitalization due to a first manic episode in patients with bipolar I disorder. Higher Clinical Global Impression-Bipolar Version-Severity scores at discharge also negatively affected rehospitalization rates., (© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.)

The aim of this study was to review the efficacy and safety of atypical antipsychotics, comparing within class, placebo, or compared to another active treatment for delirium. A literature search was conducted using PubMed, EMBASE, and the Cochrane database (1 January 1990-5 November 2012). Selection criteria for review were prospective, controlled studies (comparison studies), using validated delirium rating scales as outcome measures. A total of six prospective, randomized controlled studies were included in the review. It was found that atypical antipsychotics are effective and safe in treating delirium, even though there seemed to be no difference between each agent. In particular, comparison studies with haloperidol showed that the efficacy of atypical antipsychotics was similar to that of low-dose haloperidol. It was concluded that atypical antipsychotics appear to be effective and tolerable in the management of delirium, even though the evidence is limited., (© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.)

Aims: The goal of this study was to assess the efficacy and tolerability of tianeptine in combination with selective serotonin re-uptake inhibitor (SSRI) in partial responders or non-responders to SSRI monotherapy., Methods: In this prospective, open-label, 6-week study, 150 patients with major depressive disorder who had previously not responded or partially responded to SSRI monotherapy were recruited. Tianeptine was given in combination with an SSRI for 6 weeks., Results: Significant improvements were observed in the mean scores of the Hamilton Depression Rating Scale (HDRS), Montgomery-Åsberg Depression Rating Scale (MADRS), and Clinical Global Impression-Severity (CGI-S). The change in the mean HDRS, MADRS, and CGI-S scores was significant from week 1. The response rates were 64.7% (HDRS) and 68.7% (MADRS), and the remission rates were 34.0% (HDRS) and 42.0% (MADRS) at week 6. Thirty-six patients (24.0%) reported adverse events that were determined by the investigator to be related to one of the study drugs. The tianeptine and SSRI combination was generally well-tolerated., Conclusions: A combination strategy with tianeptine may be an effective and well-tolerated tool for patients who have failed to adequately respond to SSRI monotherapy., (© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.)

The objective of the present study was to evaluate changes in platelet counts on three different kinds of antidepressant. All subjects (n = 131) in their drug-naïve state had been diagnosed with depression. Escitalopram (n = 42), venlafaxine (n = 50) and bupropion (n = 39) were prescribed, and platelet count was measured before and after 1 month of treatment and compared. Decrease in platelet count on escitalopram was significant, while the others were not. These findings suggest that escitalopram may be associated with decreased platelet count, and bupropion is less likely to exert an influence on platelet count., (© 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.)

Aims: The goal of the present study was to evaluate the efficacy of risperidone combined with mood stabilizers for treating bipolar mixed state., Methods: The present study was a 24-week, open-label, combination, prospective investigation of the efficacy of risperidone in combination with mood stabilizers. Risperidone (1-6 mg/day) was given in combination with mood stabilizers in flexible doses according to clinical response and tolerability for 114 patients in mixed or manic episode., Results: Forty-four patients met our criteria for mixed state bipolar disorder and 70 met the criteria for pure mania. Mean age for the subjects was 39.0 +/- 11.0 years and 55.3% were female. The combination of risperidone with mood stabilizers significantly improved the scores on the Young Mania Rating Scale (YMRS), 17-item Hamilton Rating Scale for Depression (HAMD), 18-item Brief Psychiatric Rating Scale (BPRS), Global Assessment Scale (GAS), and Clinical Global Impression Scale for use in bipolar illness Severity (CGI-BP) at 24 weeks (P < 0.0001). Analysis of the YMRS, BPRS, GAS, and CGI-BP scores showed significant improvement in both the manic and mixed groups. The rate of response in YMRS scores was 84.2% (n = 96) and the rate of YMRS remission was 77.2% (n = 88) at week 24 in the total population. Seventy-four patients met both YMRS < or = 12 and HAMD < or = 7 at week 24 (64.9%). Risperidone was well tolerated, and adverse events were mostly mild., Conclusion: The combination of risperidone with mood stabilizers was an effective and safe treatment for manic symptoms and coexisting depressive symptoms of bipolar disorder.

This trial was to evaluate the efficacy and tolerability of venlafaxine extended release (XR) and paroxetine for treatment of patients with generalized anxiety disorder (GAD). Sixty patients who met DSM-IV criteria for GAD were randomly assigned to either venlafaxine XR or paroxetine for 8 weeks. Efficacy was assessed with the Hamilton Rating Scale for Anxiety (HAM-A) and Clinical Global Impression-Severity of Illness (CGI-S) scale at the baseline, week 1, week 4, and week 8. The side-effects were collected with reported adverse events and laboratory tests throughout the study period. Repeated measures analysis of variance (ANOVA) on the HAM-A and CGI-S scores showed a significant decrease over time in both treatment groups without significant group difference or time x group interaction effect. There were no serious adverse events in both groups. This open trial demonstrated that either venlafaxine XR or paroxetine would be effective and tolerable for the treatment of patients with GAD. Double blind, placebo-controlled head-to-head comparison studies are needed to draw a definite conclusion.

Few studies for the long-term effects of antidepressants on post-traumatic stress disorder (PTSD) have been conducted. The aim of the present study was to investigate the effectiveness of mirtazapine during the 24-week continuation treatment in patients with PTSD. Out of 15 patients who participated in the previous 8-week short-term study, 12 patients completed 24-week continuation treatment with mirtazapine. The effectiveness was evaluated at week 12 and week 24 using Impact of Event Scale-Revised (IES-R), Short PTSD Rating Interview (SPRINT), Interviewer-Administered Structured Interview for PTSD (SIP) and Montgomery-Asberg Depression Rating Scale (MADRS). The tolerability of continuation treatment was also reported. The scores on the IES-R, SPRINT, SIP and MADRS were significantly reduced over time from baseline to week 24, the end-point (F=36.1, d.f.=4, P<0.001; F=106.3, d.f.=4, P<0.001; F=121.1, d.f.=4, P<0.001; F=198.9, d.f.=4, P<0.001). On post-hoc analysis, the scores of all four measures were significantly reduced at the end point since week 8. However, after Bonferroni's correction, that was statistically significant in SPRINT only. The number of patients whose scores were reduced over 50% in all four scales had a tendency of incremental increase from three at week 8 to eight at the end point (P=0.063). No serious drug-related side-effects occurred. These results suggest that the mirtazapine may be effective in the continuation treatment of PTSD as well as short-term treatment. Further and better-designed studies are necessary.

The purpose of the present paper was to investigate the effects of the dopamine agonist amantadine in those patients with weight gain induced by olanzapine. An open trial was conducted in those patients who gained >3 kg in weight induced by olanzapine use. All subjects were evaluated by weight, body mass index (BMI), the Brief Psychiatric Rating Scale (BPRS), and the Extrapyramidal Symptom Rating Scale (ESRS) before and after the use of amantadine in addition to olanzapine. Twenty-five of 30 enrolled patients completed the present study. Mean bodyweight and BMI was increased by 6.44 +/- 4.42 kg and 5.04 +/- 3.47 kg/m2 significantly with olanzapine alone (P < 0.001). When amantadine and olanzapine were used together, the average weight and BMI decreased by 1.07 +/- 3.19 kg and 0.84 +/- 2.5 kg/m2, but did not have statistical significance. The average values of BPRS showed a significant decrease (P < 0.001). No significant changes were present in ESRS. Amantadine did not have an effect on weight gain induced by olanzapine. Randomized placebo-controlled prospective studies are needed.

The purpose of the present paper was to investigate the relationship between the first exon at position +49 (A/G) polymorphism of the cytotoxic T lymphocyte antigen 4 (CTLA4) gene and bipolar disorder. Among the Korean patients diagnosed with bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV), 90 patients without serious medical illness, neurologic illness, hormonal disorder, or concomitant mental illness were selected. The normal control group consisted of 149 age- and sex-matched subjects without current or past history of autoimmune diseases or mental disorder. DNA was extracted from peripheral blood using proteinase K; and the exon 1 region of the CTLA4 gene was amplified by polymerase chain reaction. Gene typing was performed using single strand conformation polymorphism. There were no significant differences in genotype frequencies of CTLA4*G/G, CTLA4*G/A, and CTLA4*A/A between the patients with bipolar disorder and the control group (48.9% vs 46.3%, 44.4% vs 39.6%, and 6.7% vs 14.1%, respectively). There were no significant differences in allelic frequencies of CTLA4*G and CTLA4*A between the patients with bipolar disorder and the control group (71.1% vs 66.1%; 28.9% vs 33.9%, respectively). In the present study an association was not found of exon 1 (+49) polymorphism of CTLA4 gene with bipolar disorder in the Korean population.

The purpose of the present study was to examine the association between the tumor necrosis factor (TNF)-alpha gene (A) polymorphism and schizophrenia in a Korean sample of schizophrenic patients and control subjects. Genotyping for the TNFA polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele distributions of the TNFA polymorphism between schizophrenic patients and controls were not significantly different. In the light of these results, the TNFA polymorphism seems not to confer susceptibility to the pathogenesis of schizophrenia, at least in the Korean population.

The purpose of the present paper was to investigate the interleukin (IL)-4 promoter gene -590 and receptor alpha (Ralpha) gene 1902 polymorphism in Korean schizophrenic patients. A total of 222 Korean patients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) and 165 normal healthy controls participated in the present study. The DNA was extracted from whole blood using proteinase K, and the IL-4 promoter and receptor gene were amplified by polymerase chain reaction. The genotype was determined using single-strand conformation polymorphism (SSCP) analysis. The distribution of the alleles and genotypes in patients with schizophrenia was not significantly different from those of controls. In conclusion, these results suggest that the polymorphisms in IL-4 promoter gene -590 and IL-4 Ralpha gene 1902 are not involved in the pathophysiology of schizophrenia in the Korean population.

Tumor necrosis factor (TNF)-beta has been implicated in the regulation of immune system. Alterations of the immune system in patients with major depressive disorder (MDD) have been also proposed to date. The present study was undertaken to investigate whether TNF-beta gene polymorphism is associated with MDD in the Korean population. Ninety-five patients with MDD who met the criteria of DSM-IV and 202 gender- and age-matched unrelated volunteers participated in the study. Genotyping for TNF-beta gene was performed by a polymerase chain reaction-restriction fragment length polymorphism method. The genotype and allele distribution in patients with MDD was similar to that of the controls. This study suggests that the TNF-beta gene polymorphism does not confer a susceptibility to MDD in the Korean population. A larger scaled study to examine different races is necessary to determine a role in the pathogenesis of MDD.

This retrospective naturalistic study, conducted on patients with schizophrenia, was undertaken to examine the differences in the clinical characteristics of subjects who were treated with risperidone, but who were discontinued soon after administration, and those who were maintained on the drug for a long-term period. Data on 210 of 580 inpatients with schizophrenia who were treated with risperidone and whose complete medical records were available, were analyzed. Patients maintained on risperidone for at least 2 years were assigned to a 'long-term maintenance' (LTM) group and those who were discontinued within 6 months of risperidone administration were assigned to an 'early drop-out' (ED) group. The parameters used for comparisons included the patients' demographic characteristics, the presence/absence of physical or psychiatric comorbidities, the severity of the psychopathology, the typology of the schizophrenia, the nature and subjects' responses to previous antipsychotic treatments (if any) and dosages of risperidone treatment. Of the 210 subjects, 67 (31.9%) belonged to the ED group, whereas 143 (68.1%) were maintained on risperidone at 2 years. There were no significant differences in the demographics, nor in the severity of the psychopathology, nor were there significant differences in the starting or maximal dosages of risperidone administered between the two groups. Exposure to any previous antipsychotic and the longest maintained final dosage of risperidone were significantly different in the two groups. We believed that a multicenter-based retrospective naturalistic study would provide useful information about the efficacy and other practical aspects of antipsychotic administration.

Little is known about the arachnoid cyst and there have been few reports of it accompanying psychiatric disturbances. A 57-year-old patient was admitted due to sudden headache, auditory hallucination, and delusion of persecution. An arachnoid cyst was found in the anteromedial aspect of middle cranial fossa on his magnetic resonance image. This was his first psychotic episode and he was also negative to other clinical evaluations including endocrine system. His psychotic symptoms were suspected to be induced by the arachnoid cyst and it was well controlled by low-dose risperidone administration. He left hospital free from psychotic symptoms on 14th hospital day.

The present study was carried out to examine the relationship of interleukin (IL)-10 gene polymorphism at position -819 for major depression and schizophrenia in the Korean population. DNA was extracted from 92 Korean patients with major depression, 141 Korean patients with schizophrenia, and 146 ethnically matched controls. DNA was amplified by a polymerase chain reaction-based method and digested by MaeIII, and the restriction fragment length polymorphism of two alleles, IL-10*C and IL-10*T, were assessed. There were no significant differences in genotype frequencies of IL-10*T/T, IL-10*T/C, and IL-10*C/C as well as allelic frequencies of IL-10*T and IL-10*C between patients with major depression and controls in the Korean population. Comparison of genotype and allelic frequencies of IL-10 gene between patients with schizophrenia and controls were also not significant. The present study suggests that IL-10 gene polymorphism at position -819 does not confer susceptibility to major depression and schizophrenia, at least in the Korean population. Further systematic studies including various clinical variables would be required.

This study was performed to assess the efficacy and safety of olanzapine for the treatment of delirium in a Korean population. An open trial of olanzapine was conducted in Korean patients with delirium caused by multiple medicosurgical conditions. All subjects were evaluated by Delirium Rating Scale (DRS), which is known to be one of the most sensitive scales for delirium. In addition, other data for profiles of side-effects were collected and analyzed. Twenty patients were treated by olanzapine with doses of 5.9 +/- 1.5 mg/day. The initial dose was 4.6 +/- 0.9 mg/day and maximal dose of olanzapine was 8.8 +/- 2.2 mg/day. The average duration of treatment was 6.6 +/- 1.7 days and the day of maximal response was 3.8 +/- 1.7 treated days. The scores of DRS were significantly improved from 20.0 +/- 3.6 at the time of pretreatment to 9.3 +/- 4.6 at the post-treatment. All subjects showed no definite serious side-effects including anticholinergic and extrapyramidal symptoms. Olanzapine treatment for patients with delirium was effective and safe. This newer drug may be a useful alternative agent to classical antipsychotics in the treatment of delirium.

This study was carried out to verify the relationship between major depression and cytotoxic T lymphocyte antigen-4 (CTLA-4), which is related to immunological function such as T-cell regulation. Among the Korean patients diagnosed with major depression according to DSM-IV, 77 patients without neurological illness, hormonal disorder, or comorbid mental illness were selected. The stored data on 149 normal Koreans from the Catholic Hemopoietic Stem Cell Bank of Korea, were used as a control group. The data of the Korean control group were compared with those of the studies of different ethnic groups. DNA was extracted from whole blood using proteinase K and the exon 1 region of CTLA-4 gene was amplified by polymerase chain reaction. Gene typing was performed using single strand conformation polymorphism. The results were assessed. There were significant differences in frequencies of CTLA-4 allele (chi2 = 56.472, d.f. = 1, P = 0.001) and genotype (chi2 = 46.132, d.f. = 2, P = 0.001) between the Korean population and the Caucasian population. However, we could not find any differences between the Korean and the Japanese population. There were no significant differences in genotype frequencies of CTLA-4*G/G, CTLA-4*G/A, and CTLA-4*A/A between the patients with major depression and the control group in the Korean population (48.1% vs. 46.3%, 41.6% vs 39.6%, 10.3% vs. 14.1%, respectively). There were no significant differences in allelic frequencies of CTLA-4*G and CTLA-4*A between the patients with major depression and the control group in the Korean population (68.8% vs. 66.1%, 31.2% vs. 33.9%, respectively). Although the present study produced negative results for the association of exon 1 polymorphism of CTLA-4 gene with major depression in the Korean population, further systematic research, including diverse clinical variables, would be necessary.