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We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention., Competing Interests: Declaration of competing interest Min Seo Kim, Hye Chang Rhim, Ariel Park, Hanna Kim, Kyu-Man Han, Ashwin A. Patkar, Chi-Un Pae, and Changsu Han have no commercial associations that may present a conflict of interest in relation to this manuscript., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common and a debilitating neuro-behavior disorder in the pediatric population. Although numerous effective psychostimulants are available, more than 30% of patients still do not show adequate treatment response rendering diverse pharmacological options. We aimed at assessing the efficacy and safety of modafinil in the treatment of children and adolescents with ADHD by conducting a meta-analysis. An extensive search of databases and clinical trial registries resulted in five published short-term randomized, double-blind, placebo-controlled trials. Primary efficacy measures were mean change in ADHD Rating Scale-IV Home (ADHD-RS-IV Home) and School Version (ADHD-RS-IV School) from baseline to study end point. The results showed that modafinil more significantly improved ADHD-RS-IV Home (SMD, -0.77 [95%CI, -1.11 to -0.44]) and School (SMD, -0.71 [95%CI, -0.96 to -0.47]) than placebo. Dropout rate due to adverse event did not significantly differ between two groups. In terms of commonly observed side effects, modafinil showed significantly higher incidence of decreased appetite (RR = 5.02, 95% CIs, 2.55 to 9.89, P < 0.00001) and insomnia (RR = 6.16, 95% CIs, 3.40 to 11.17, P < 0.00001). Modafinil did not cause a clinically significant increase of heart rate, systolic blood pressure, and diastolic blood pressure. Although we found that modafinil may be another treatment option in children and adolescents with ADHD, the results should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of clinical trials., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

No study has directly compared the efficacy and tolerability of aripiprazole augmentation (AA) and antidepressant switching (SW) in patients with major depressive disorder (MDD). This is the first 6-week, randomized, rater-blinded, direct comparison study between AA and SW in outpatients. An inadequate response to antidepressants was defined as a total score ≥ 14 on the Hamilton Depression Rating Scale-item 17 (HDRS-17) despite adequate antidepressant dosage for at least 6 weeks in the current depressive episode. The primary endpoint was change in the total score of the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the end of treatment. Secondary efficacy measures included the response and remission rates as priori defined at the end of treatment: changes in total scores of the HDRS-17, Iowa Fatigue Scale (IFS), and Sheehan Disability Scale (SDS) from baseline to the end of treatment and the proportion of patients who scored 1 or 2 on the Clinical Global Impression-Improvement Score (CGI-I) at the end of treatment. Tolerability was assessed with the Barnes Akathisia Rating Scale (BARS) and Arizona Sexual dysfunction scale (ASEX), and the numbers of adverse events were compared between the two groups. A total of 101 patients were randomized to either AA (n = 52) or SW (n = 49). The mean change in the MADRS score from baseline was significantly higher in the AA, with a difference in magnitude of -8.7 (p < 0.0001). The intergroup difference was first evident in week 2. The numbers of responders (p = 0.0086) and remitters (p = 0.0005) were also significantly higher in the AA (60% and 54%, respectively) compared with the SW (32.6% and 19.6%, respectively). On most secondary endpoints, AA showed better clinical outcomes compared to SW. The tolerability profiles were comparable between the two groups. Overall, AA yielded potentially beneficial clinical outcomes compared to SW. Given the methodological shortcomings of the present study, adequately powered, more rigorously controlled clinical trials are strongly warranted to confirm the present findings., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Vortioxetine has a beneficial pharmacological profile for reducing anxiety and depression. Recently, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with generalized anxiety disorder (GAD); however, the results from GAD RCTs are inconsistent. With an extensive search of databases and clinical trial registries, four published short-term RCTs were identified and included in the present meta-analysis. The mean change in total scores on the Hamilton Anxiety Rating Scale (HAMA) from baseline was the primary endpoint. The secondary endpoints included the response and remission rates, as defined by a ≥50% reduction in HAMA total scores and a ≤7 change in the HAMA total score at the end of treatment. In addition, the mean change in the HAMA total score from baseline in the subgroup with a HAMA total score ≥25 at baseline was included. Vortioxetine was significantly more effective than was placebo, with a standardized mean difference (SMD) of -0.118 (95% CIs, -0.203 to -0.033, P = 0.007). In particular, those with severe GAD (HAMA total score ≥25 at baseline) had a significantly greater benefit from vortioxetine than those without (SMD = -0.338, 95% CIs = -0.552 to -0.124, p = 0.002). The odds ratios (ORs) for vortioxetine for response and remission were 1.221 (95% CIs, 1.027 to 1.452, P = 0.024) and 1.052 (95% CIs, 0.853 to 1.296, P = 0.637), respectively. Discontinuation due to adverse events (AEs) (OR = 1.560, 1.006 to 2.419, p = 0.047) was marginally higher in vortioxetine than placebo treatment, whereas discontinuation due to any reason (OR = 0.971, 0.794 to 1.187, p = 0.771) and inefficacy (OR = 0.687, 0.380 to 1.243, p = 0.215) were not significantly different among treatment groups. Although our results suggest that vortioxetine may have a potential as an another treatment option for GAD (especially for severe GAD), they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of RCTs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Despite the fact that the majority of currently available treatment guidelines propose antidepressants as the first-line pharmacological therapy for posttraumatic stress disorder (PTSD), a substantial portion of patients fail to show an adequate response following this type of treatment. In this context, a number of small, open-label studies and randomized controlled clinical trials (RCTs) have found atypical antipsychotics (AAs) to be a beneficial treatment for patients with PTSD. Thus, the present meta-analysis was conducted to enhance the sample size power and further the current understanding of the role of AAs for the treatment of PTSD. An extensive search of several databases identified 12 appropriate RCTs and available data from 9 of these (n = 497) were included in the final meta-analysis. AAs may have potential benefits for the treatment of PTSD as indicated by changes from baseline of the total score on the Clinician Administered PTSD Scale (CAPS; standardized mean difference [SMD] = -0.289, 95% confidence intervals [CIs] = -0.471, -0.106), P = 0.002). Additionally, AAs were found to be significantly more effective (P < 0.0001) than a placebo in terms of change from baseline for the intrusion sub-score on the CAPS (SMD = -0.373, 95% CIs = -0.568, -0.178) but there were no significant reductions for the avoidance and hyperarousal sub-symptoms. The responder rate and rate of improvement of depressive symptoms were also significantly higher in the AA group than the placebo group (P = 0.004 and P < 0.0001, respectively). However, the present results should be interpreted carefully and be translated into clinical practice only with due consideration of the limited quality and quantity of existing RCTs included in this analysis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Despite numerous antidepressants available, many patients with depression do not achieve adequate response rendering needs for novel antidepressants with different mechanism of actions. Acetyl-l-carnitine (ALC) is a potential antidepressant with novel mechanism of action because of its diverse functions related with neuroplasticity. Animal and cellular models suggest that ALC's neuroplasiticity effect, membrane modulation, and neurotransmitter regulation may play an important role in treatment of depression. Four randomized clinical studies (RCT) demonstrated the superior efficacy of ALC over placebo (PBO) in patients with depression. Two RCTs showed its superior efficacy over PBO in dysthymic disorder, and 2 other RCTs showed that it is equally effective as fluoxetine and amisulpride in treatment of dysthymic disorder. ALC was also effective in improving depressive symptoms in patients with fibromyalgia and minimal hepatic encephalopathy. It was also found to be equally tolerable to PBO and better tolerable than fluoxetine and amisulpride. In conclusion, ALC may be potentially effective and tolerable next treatment option with novel action mechanisms for patients with depression, in particular older population and patients with comorbid medical conditions who are vulnerable to adverse events from antidepressants. However, more clinical trial data with adequately-powered, well-designed and advanced methodology will be mandatory to conclude whether ALC as a monotherapy or augmentation agent may be efficacious and clinically beneficial for depression., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: This study investigated the association of personality traits with the baseline clinical characteristics and treatment outcomes of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)., Methods: Subjects were evaluated at baseline and at week 12 following routine treatment for CP/CPPS using the Korean version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) to measure the severity of CP/CPPS; the Korean version of the Patient Health Questionnaire-9 (PHQ-9) to assess depression; the Korean version of the Patient Health Questionnaire-15 (PHQ-15) to evaluate somatization; and the Korean version of the EuroQol Questionnaire-5 Dimensions (EQ-5D), specifically the EQ-5D utility index and the EQ-5D visual analog scale (EQ-5D VAS), to assess quality of life (QoL). Personality traits including extraversion, agreeableness, conscientiousness, neuroticism, and openness were determined at baseline using the 44-item Big Five Inventory (BFI). The influence of personality traits on the clinical characteristics and treatment outcomes of patients with CP/CPPS was assessed using relevant statistical analyses., Results: Neuroticism was associated with a significantly poorer treatment response and higher levels of depression and somatization. Extraversion, agreeableness, and conscientiousness had some influence on clinical characteristics but openness did not affect overall symptoms or the treatment response in patients with CP/CPPS., Conclusions: We found that neuroticism may be the most important personality trait associated with treatment response and the severity of depression and somatization in patients with CP/CPPS. However, our exploratory findings should be confirmed by additional studies with adequate power and improved designs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

There has been no studies comparing the clinical benefits of aripiprazole augmentation (AT), antidepressant combination (AC), and switching to a different antidepressant (SW) in patients with major depressive disorder (MDD) patients partially or not responding to an initial antidepressant. AT, AC, or SW was chosen by patients. The primary efficacy measure was the proportion of patients showing an improvement in the Clinical Global Impression-Clinical Benefit (CGI-CB) score at week 8. Secondary efficacy measures included changes in CGI-CB, CGI-Severity (S) and subjective satisfaction scores. Remission and responder analysis were also employed. A total of 295 patients were enrolled. The most preferred strategy was AT (n = 156, 52.9%), followed by AC (n = 93, 31.5%) and SW (n = 46, 15.6%). The improver was significantly higher in AT (74.1%) compared with AC (48.1%; p < 0.001) and similar to SW (73.5%, p = 0.948), whereas no significant difference was found between AC and SW. Similar results were also found in the most secondary endpoint measures proving a superiority of AT over AC without differences between AT and SW. Tolerability profiles were similar across the three groups; however, the mean weight gain for SW (-0.1 kg) was significantly less than that for AC (1.3 kg, p < 0.05). Patients preferred AT to AC or SW when an antidepressant was ineffective in treating their depression. Among the three treatment strategies, overall AT yielded greater clinical benefit than did AC and SW. Adequately powered, well-controlled clinical trials are strongly warranted to confirm our findings due to methodological shortcomings., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The brain is an organ predisposed to oxidative/nitrosative stress. This is especially true in the case of aging as well as several neurodegenerative diseases. Under such circumstances, a decline in the normal antioxidant defense mechanisms leads to an increase in the vulnerability of the brain to the deleterious effects of oxidative damage. Highly reactive oxygen/nitrogen species damage lipids, proteins, and mitochondrial and neuronal genes. Unless antioxidant defenses react appropriately to damage inflicted by radicals, neurons may experience microalteration, microdysfunction, and degeneration. We reviewed how oxidative and nitrosative stresses contribute to the pathogenesis of depressive disorders and reviewed the clinical implications of various antioxidants as future targets for antidepressant treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Gender differences in various clinical features of schizophrenia have been noted and estrogen has been regarded to play important roles. A few previous studies on the association between estrogen receptor (ER) genotypes and schizophrenia focused mainly on ER α gene but failed to report consistent results. The present study was designed to analyze the differences in the frequencies of both ERα and ERβ gene polymorphisms in subjects with schizophrenia compared to healthy controls among Korean population. Moreover, we investigate the association between different genotypes of ER genes and various clinical variables of schizophrenia. We observed that PvuII and XbaI polymorphisms of ERα gene showed significant differences between patients with schizophrenia and control groups (p=0.006). Among clinical variables, only the age of onset was related to RsaI genotype of ERβ gene (p=0.039). In conclusion, the present study suggests that ERα gene polymorphisms may be associated with the pathogenesis of schizophrenia and RsaI AA genotype of ERβ might have protective effect on age at onset of schizophrenia in Korean patients with schizophrenia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate weight gain and its potential risk factors among different second generation antipsychotics (SGAs). The study was conducted for Korean inpatients with schizophrenia in a university hospital in Seoul, between Jan 2000 and Dec 2007. Data were collected by reviewing the medical records of the patients, who were prescribed to one of the SGAs among aripiprazole, olanzapine, quetiapine or risperidone. The changes of weight and body mass index (BMI); risk of clinically significant weight gain (>7% gain to initial weight) and their associations with various clinical characteristics of such patients were analyzed. Five hundred and eighty-eight (588) and 294 subjects treated with one of the four SGAs for a duration of 1 month and 2 months were included, respectively. Olanzapine showed significantly greater weight and BMI increase at month 1 (p=0.028 for weight; p=0.019 for BMI) and month 2 (p=0.032 for weight; p=0.029 for BMI) than others. Females showed greater BMI increase change (0.70±0.91 kg/m(2), p=0.008) and were also more likely to experience clinically significant weight gain (odd ratio=1.846, 95% CI=1.098 to 3.105, p=0.021) at month 1. Younger patients (<45 years old) had significantly greater weight and BMI increase at both months 1 and 2. Younger patients also showed greater risk for clinically significant weight gain at month 2 (odd odd ratio=2.567, 95% CI=1.196 to 5.508, p=0.016). Low baseline BMI (<25 kg/m(2)) was associated with greater weight gain at month 1 (1.92±2.29 kg, p<0.001) and month 2 (4.07±3.56 kg, p<0.001) and BMI increase at month 1 and month 2 (p<0.001 for both). Patients with low baseline BMI showed higher risk of clinically significant weight gain at both months 1 and 2 (p<0.001 for both). Olanzapine was shown to have higher metabolic risk than other SGAs in inpatients with schizophrenia. The individual's own clinical characteristics also exerted influence on weight gain effects of SGAs. Younger patients with lower baseline BMI were under greater risk of antipsychotic-induced weight gain. More studies are required to verify the role of gender on weight gain., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Quetiapine fumarate extended release (XR) has been approved for treatment of schizophrenia and bipolar disorder. Quetiapine may have antidepressant effects through effects on 5-HT(2A) receptor, 5-HT(1A) receptor, dopamine receptor, glutamate receptor and norepinephrine transporter. Recently, 7 large-scale randomized, double-blind, placebo (2-studies with active comparator)-controlled clinical trials have demonstrated that quetiapine XR has clinically meaningful efficacy as monotherapy and adjunct therapy to antidepressants for the treatment of adult patients with major depressive disorder (MDD). In such clinical trials, quetiapine XR was generally well tolerated, although weight gain and changes in metabolic parameters, consistent with the known profile of quetiapine, were observed in some patients. As of December 2009, the United States Food and Drug Administration has approved quetiapine XR for the adjunct treatment of MDD. From the data of currently available clinical trials, this review provides an overview of the data and clinical implications for quetiapine XR in the treatment of MDD to enhance clinicians understanding of the use of quetiapine XR in the treatment of MDD., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Despite of a high comorbidity of depressive and/or anxiety disorders with fibromyalgia, information on the clinical implications of this comorbidity is limited but antidepressants are commonly prescribed to treat fibromyalgia in clinical practice. We investigated whether a history of depressive and/or anxiety disorders was associated with response to paroxetine controlled release (CR) in the treatment of fibromyalgia., Methods: One hundred sixteen (116) fibromyalgia subjects were randomized to receive paroxetine CR or placebo for 12 weeks. The primary outcome was treatment response defined as >or=25% reduction in the Fibromyalgia Impact Questionnaire (FIQ) score. In multivariate logistic regression, we determined if a history of depression and/or anxiety disorders was an independent predictor of response to paroxetine CR., Results: In logistic regression, the history of depression and/or anxiety did not predict treatment response as measured by >or=25% reduction in Fibromyalgia Impact Questionnaire (FIQ) score (OR=0.66, 95% CI=.29-1.49, Wald=0.97, p=0.32), while the drug status (paroxetine CR) was significantly associated with treatment response (OR=2.57, CI=1.2-5.61, Wald=5.5, p=0.02)., Conclusion: A significant proportion of patients with fibromyalgia had a history of anxiety and or depressive disorders. However response to treatment of fibromyalgia symptoms with paroxetine CR was not associated with a history of depressive and/or anxiety disorders. Our findings need to be confirmed in more adequately-powered and well-designed subsequent studies.

Background: There is some evidence suggesting a role of TAAR6 in schizophrenia. The aim of the present study is to investigate possible influences of a panel of markers in TAAR6 (rs8192625, rs4305745, rs4305746, rs6903874, rs6937506) on clinical outcomes and side effects in a sample of Korean schizophrenic aripiprazole treated patients., Methods: Efficacy was assessed at baseline and weeks 1, 2, 4, 6, 8 using CGI-S, CGI-I, BPRS and SANS. Side effects were evaluated through SAS, BAS and AIMS. Multivariate analysis of covariance (MANCOVA) was used to test possible influences of single SNPs on clinical and safety scores. Tests for associations using multi-marker haplotypes were performed using the statistics environment "R"., Results: A significant time per genotype interaction was found between rs4305746 in repeated measures of ANOVA on BPRS scores (F=2.45, df=10,365, p=0.008). In particular G/A and A/A genotype patients were more likely to improve over time as compared to carriers of the G/G genotype. Permutation analysis confirmed a significant effect of rs4305746 on course of BPRS scores over time (p=0.007). Haplotype analysis did not reveal any significant association with clinical and safety scores at any time., Conclusion: A possible association could exist between some genotypes in TAAR6 and response to aripiprazole. However, several limitations characterize the present work, such as small sample size, the finding related to a single scale and the possibility of false positive findings, thus further investigation is required.

Dysbindin gene has been repeatedly associated with psychiatric disorders and schizophrenia in particular. This study aimed to investigate the variants of dysbindin gene in major depressive disorder (MDD). One hundred and eighty eight patients with MDD and 350 controls were investigated for 4 variants within the dysbindin gene (rs3213207 A/G, rs1011313 C/T, rs760761 C/T, and rs2619522 A/C). Haplotype analyses revealed a significant association with MDD (p=0.0007, protective A-C-T-A and A-C-C-C haplotypes), in particular the effect was due to the rs760761 (C/T) and rs2619522 (A/C) haplotype (p=0.000026). These results suggest a protective effect of some dysbindin gene haplotypes on the development of MDD. Coupled with previous findings on schizophrenia, our finding suggests that dysbindin gene variants may have a role in the susceptibility to MDD. Adequately powered further studies in different ethnic groups are warranted.

The present study was conducted to compare the effectiveness and tolerability of fluoxetine and sertraline in the treatment of undifferentiated somatoform disorder (USD), using the Patient Health Questionnaire (PHQ-15), which was specifically designed for assessing the severity of somatic symptoms. A randomized, 12-week, open-label trial of fluoxetine (10-60 mg/d) and sertraline (25-350 mg/d) in patients with USD was conducted. Six visits, at baseline and weeks 1, 2, 4, 8, and 12, were scheduled. Assessments for effectiveness and tolerability were conducted at each visit. The primary effectiveness measure was the mean change in PHQ-15 total score, from baseline to the end of treatment. Secondary effectiveness measures were the mean changes in total scores on the Beck Depression Inventory (BDI) and the 12-item General Health Questionnaire (GHQ-12), from baseline to the end of treatment. A total of 45 subjects were enrolled; of them, 28 were randomly assigned to receive fluoxetine and 17 to receive sertraline. The total score on the PHQ-15 from baseline to the end of treatment significantly decreased in the fluoxetine (-10.7, p<0.0001) and sertraline (-10.3, p<0.0001) treatment groups, with no between-group difference (F=0.0701, p=0.7924). Overall, both treatments were well tolerated and no serious adverse event was reported. This study suggests that both agents may have a potential role in the treatment of USD. A double-blind, placebo-controlled trial and/or head-to-head comparison study with larger samples are required to draw more definite conclusions.

Trace amines and their receptors may be implicated in the pathogenesis of psychiatric disorders. Previous studies have reported association of the trace amine associated receptor 6 (TAAR6) gene with susceptibility to schizophrenia and bipolar disorder but results have not been consistent. The purpose of this study was to examine these associations in Korean patients and also to test for association of TAAR6 with susceptibility to major depressive disorder (MDD). A case control sample consisting of 281 patients with schizophrenia, 190 patients with bipolar disorder, 187 patients with MDD and 288 psychiatrically healthy control subjects, was examined. Patients with schizoaffective disorder were not included in any of the psychiatric samples. Five single nucleotide polymorphisms (SNPs: rs4305745; rs8192625; rs7452939; rs6903874 and rs6937506) were genotyped in the TAAR6 gene and in the 3' regulatory region, using pyrosequencing. SNP rs6903874 was significantly associated with schizophrenia (p = 0.012) and bipolar disorder (p = 0.004). A three SNP haplotype consisting of alleles GCT from SNPs rs7452939, rs6903874 and rs6937506, respectively, was significantly over-represented in patients with schizophrenia (p = 0.0003) and bipolar disorder (p = 0.00002). A second three SNP haplotype (GTT) derived from the same SNPs was significantly under-represented in patients with bipolar disorder (p = 0.001). The GTT haplotype associations withstand the most rigorous corrections for multiple testing. These findings strongly support association of the TAAR6 gene with susceptibility to both schizophrenia and bipolar disorder in Korean patients. Further studies are needed to confirm these findings in this and other populations and to identify functional variants in TAAR6 that may be implicated in pathogenesis.

Many monoamine oxidase inhibitors (MAOIs) have been used to treat major depressive disorder (MDD). However, the prescription of MAOIs has decreased considerably as a result of side effects such as tyramine-induced hypertensive crisis, which is also known as the 'Cheese Effect'. The drug delivery system itself can affect the bioavailability of certain drugs, which might influence the efficacy and tolerability of medications, as well as improve the compliance and reduce the incidence of recurrence and relapse. Therefore, there is a need for advanced drug delivery techniques that can evade the potentially hazardous toxic effects of the parent compound, including extended-release oral, cutaneous, intravesical and intravaginal routes, etc. In this context, the selegiline transdermal system (STS, EMSAM) was introduced with improved side effect profiles and efficacy compared with the conventional form of the selegiline oral tablet. STS allows the targeted inhibition of the monoamine A (MAO-A) and MAO-B isoenzymes with minimal effects on the MAO-A in the gastrointestinal and hepatic systems. Hence, STS can reduce the risk of interactions with tyramine-rich foods. Many fundamental clinical and preclinical studies have reported that 6 mg/24 h of STS is effective against MDD without the need for dietary restrictions with an equal efficacy and improved safety profile. In addition, STS might benefit MDD patients with atypical features or who are resistant to other antidepressants. Overall, familiarity with the properties and indications of STS will have the clinicians another option of biological treatments for MDD patients but subsequent more data including actual post-market clinical experiences will be mandatory.

This study aimed to assess the safety, tolerability, efficacy, and compliance of a risperidone long-acting injection (RLAI) formulation for the maintenance treatment of stabilized bipolar patients. A prospective, open-label trial of RLAI was conducted for 12 months. Stable bipolar patients (n=11) were switched from their existing oral antipsychotic agents to RLAI, and injections were given every 2 weeks. The assessments were performed at baseline and at 6 and 12 months of treatment by using the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity of Illness (CGI-S) scale, 17-item Hamilton Rating Scale for Depression (HAM-D), Brief Psychiatric Rating Scale (BPRS), and Extrapyramidal Symptom Rating Scale (ESRS). The satisfaction levels of subjects were evaluated at the end of the study period using a 10-point visual analog scale. Ten patients (90.9%) completed the trial, and no significant changes were seen in the YMRS, HAM-D, and BPRS scores throughout the study. CGI-S and ESRS scores were significantly decreased from the baseline to the post-12-month treatment score. Relapses were not reported by any of the participants. This result indicates that RLAI may be beneficial in the maintenance therapy of stable bipolar patients; however, an adequately powered, randomized, placebo-controlled trial is necessary to draw a definite conclusion about the role of RLAI in the maintenance treatment of bipolar patients.

In the search of predictors of antidepressant efficacy, much interest has recently focused on pro-inflammatory proteins, as they were found to be elevated during major depressives states and decreased by antidepressant drugs. In the present paper we investigated the role of the genes coding for heat-shock-70 family proteins, recently hypothesized to be activated by antidepressants and thus mediate the reduction of pro-inflammatory cytosines. One hundred and forty two hospitalised patients, affected by major depression and treated with antidepressants drugs for a major depressive episode were evaluated for depressive severity at the baseline and at the discharge and genotyped for five SNPs within the genes HSPA1L, HSPA1A and HSPA1B. Markers were not individually associated with symptom severity after treatment. Instead, we found a three markers haplotype, including SNPs within HSPA1L and HSPA1A, associated with a poorer response to antidepressant treatment (p=0.005). Single markers as well as haplotypes were not associated with other clinical features. In conclusion, genetic variants within the genes coding for HSP-70 family proteins may affect the action of antidepressants and thus their therapeutic efficacy.

Panic disorder may be associated with defective serotonin (5-HT) neurotransmission. This study was to investigate the association between the tryptophan hydroxylase (TPH) gene and a serotonin transporter gene promoter polymorphism (5-HTTLPR), with panic disorder in a Korean population. 244 Korean patients with panic disorder and the 227 controls were genotyped by a polymerase chain reaction-based method. The severity of panic disorders was assessed by number of panic attacks during the previous 1 month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). All the subjects completed the assessment measures including Spielberger State-Trait Anxiety Inventory-State (STAI-S), Spielberger State-Trait Anxiety Inventory-Trait (STAI-T), Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R), Revised Anxiety Sensitivity Index (ASI-R), Clinical Global Impression Scale--Severity of Illness (CGI-S), Panic Disorder Severity Scale (PDSS), and the Hamilton Depression Rating Scale (HAMD). Responder analyses were conducted based on changes in CGI-I scores after 10 weeks of treatment. We found no significant differences in the genotype and allele frequencies in TPH A218C and 5-HTTLPR polymorphisms between the panic patients and the control group. Subgroup analyses in terms of comorbidities, response, and other primary clinical variables, indicated no differences in these polymorphisms. Our findings suggest that the TPH A218C polymorphism and 5-HTTLPR play no significant roles in the pathogenesis and clinical symptomatologies, at least in a Korean population.

This study evaluated the overall effectiveness and tolerability of atypical antipsychotics (risperidone vs. olanzapine vs. quetiapine) used in the treatment of bipolar inpatients. After screening 463 patients, the medical records of 158 inpatients with bipolar I disorder, who were given olanzapine, risperidone or quetiapine as adjuncts to mood stabilizers for at least 1 month and not administered with any other antipsychotics, were examined. Details of the tolerability and effectiveness were reviewed according to the treatment records during their hospital stay. The results showed equivalent effectiveness based on the Clinical Global Impression (CGI) and Global Assessment Functioning (GAF) score between the three atypical antipsychotics. The frequency of the extrapyramidal symptom-related side effects were higher in the risperidone-treated group than in the olanzapine and quetiapine-treated group. This suggests that risperidone, olanzapine and quetiapine have a comparable effectiveness in inpatients with bipolar I disorder in a naturalistic setting. However, there were some differences in tolerability between these results as reported from previous Western studies.

Major depressive disorder and alcohol dependence are common and serious mental illnesses. There is a great interest in discovering useful treatments for both mood symptoms and alcohol abuse in those patients with depressive disorders and comorbid alcohol dependence. The primary purpose of this study was to evaluate the effectiveness and tolerability of mirtazapine for the treatment of patients with alcohol dependence comorbid with a depressive disorder in an open label, naturalistic multicentre treatment setting. The 17-item Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS) and the Clinical Global Impression-Severity (CGI-S) scale were measured at baseline and at weeks 4 and 8 for the assessment of treatment effectiveness. Alcohol craving was measured using the Obsessive Compulsive Drinking Scale (OCDS) and the Visual Analog Scale for Craving (VAS). This study showed a statistically significant reduction of the scores on the HDRS (13.9+/-7.3, p<0.0001), HARS (10.8+/-7.2, p<0.0001) and the CGI-S (1.7+/-1.0, p<0.0001) from baseline to the endpoint (week 8). The OCDS and VAS scores were also decreased significantly by 42.3% and 53.2% (9.0+/-10.0, p<0.0001; 2.5+/-2.4, p<0.0001, respectively). The number of patients with a 50% reduction or more in the HDRS and HARS scores was 103 (72.0%) and 106 (74.1%) at the endpoint, respectively. Adverse events related to mirtazapine were observed in 10% or more of the patients in this study. In conclusion, the results from this naturalistic study suggest that the use of mirtazapine for the patients with alcohol dependence comorbid with depressive disorder is accompanied by clinical improvement in their mood and alcohol craving.

This study examined the relationship between a MnSOD gene (MnSOD) polymorphism (Ala-9Val) and mood disorders such as major depressive disorder (MDD) and bipolar I disorder (BD). Eighty patients with BD, 61 patients with MDD and 106 healthy controls were enrolled in this study and genotyped using a polymerase chain reaction-based method. The patients with MDD and BD, and the controls had a similar distribution of the genotypes and alleles in the Ala-9Val MnSOD polymorphism. The combined analysis (MDD plus BD) also failed to find any association between the Ala-9Val MnSOD polymorphism and mood disorders. Subgroup analyses according to the clinical variables such as the family history, age at onset, psychotic features and suicide history failed to identify any association with the Ala-9Val MnSOD polymorphism. This preliminary data suggests that at least in the Korean population, the Ala-9Val MnSOD polymorphism is not associated with the development of mood disorders or their clinical parameters. However, more study with a larger population sample will be needed.

The antagonism of 5-HT3 receptor by mirtazapine results in an antiemetic effect, suggesting that mirtazapine could be considered a successful antiemetic agent in patients suffering from severe nausea and vomiting. There have been several reports of successful mirtazapine treatment for nausea or vomiting from secondary causes but cases of primary severe nausea and vomiting are still lacking, in particular, there are no reported cases in Asians. The authors report two cases with severe nausea and vomiting that were dramatically treated with mirtazapine in the Korean population.

This study evaluated the clinical variables associated with the early administration of antipsychotics for the treatment of bipolar mania. 63 out of 97 inpatients with bipolar I disorder according to the DSM-IV criteria and who were consecutively admitted to the Kangnam St. Mary's Hospital, between September 2002 and March 2004, were included in the study. Regression analysis was run on the clinical variables in order to identify the factors affecting the early administration of antipsychotics. The route of admission and exposure to antipsychotics at the last follow-up were found to be associated with the early administration of antipsychotics (odds ratios=33.0 and 13.1, respectively). This study suggests that some clinical factors in bipolar mania might be linked to the earlier antipsychotic treatment. However, more studies will be needed to confirm this finding.

This study investigated the association between the serotonin transporter polymorphism (5-HTTLPR) and alcoholism in the Korean population. In addition, in order to reduce the clinical heterogeneity, sub-analysis was carried out according to some clinical variables such as a family history of alcoholism, aggressive/violent behavior and the age of onset of alcoholism. One hundred and forty-five patients meeting the DSM-VI criteria for alcohol dependence and 201 healthy controls were examined. Genotyping was performed using a polymerase chain reaction (PCR)-based method. The frequency of the L-allele of 5-HTTLPR was significantly higher in the alcohol dependent patients than in the normal controls (chi(2)=19.11, df=1, p<0.001). Furthermore, there was a significant difference in the allelic distribution between the subgroups defined by a family history of alcoholism (chi(2)=4.005, df=1, p=0.045). This study suggests a putative role of the 5-HTTLPR for alcoholism in the Korean population. However, a replication study with larger different ethnic samples and a refinement of the subtype of alcoholism is needed.

This study evaluated the overall effectiveness and tolerability of adjunctive quetiapine as a continuation therapy for the long-term treatment of bipolar mania. Twenty-three patients were enrolled in this study and received quetiapine add-on treatment in combination with their existing or new mood stabilizers. The clinical assessment was carried out using the Young Mania Rating Scale (YMRS), Clinical Global Impression-severity(CGI-s), Hamilton Depression Rating Scale scores-17 item, Simpson-Angus Rating Scale and Barnes Akathisia Rating Scale at the baseline, 1, 4, 12 and 24 weeks. The YMRS and CGI-s decreased significantly from the baseline to the endpoint by 89.7% and 78.3%, respectively (p < 0.0001; p < 0.0001). By the end of the study, 22 patients showed at least 50% improvement in the YMRS score. This study suggests that quetiapine can be used as an adjunct in the long-term treatment of bipolar mania.

Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania. The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting. Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study. In order to assess the efficacy and the extrapyramidal symptoms (EPS), the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at the baseline and at weeks 1, 3 and 6. From the baseline to the endpoint, the YMRS and CGI scores were reduced by 67.9% and 56.6% in the topiramate plus risperidone group (TPMG). The YMRS and CGI scores were also reduced by 63.7% and 58.2% in the divalproex plus risperidone group (DVPG). The weight and body mass index (BMI) increased significantly by 3.6% and 3.3% from the baseline to the endpoint in the DVPG, while they decreased by 0.5% and 0.4%, respectively, with no significant difference in the TPMG. There were no serious adverse events in either group. Despite the methodological limitations, topiramate was effective and tolerable for treating acute mania and may also be a promising alternative to a weight-gain liable mood stabilizer (MS) such as divalproex.

Membrane phospholipid abnormalities have been proposed to be involved in the pathogenesis of schizophrenia. Cytosolic phospholipase A2 (cPLA2) plays a major role in the metabolism of fatty acids but is also found in abnormalities in patients with schizophrenia. This study examined the association between the cPLA2 gene BanI polymorphism and schizophrenia. Ninety-seven Korean schizophrenia patients and 117 healthy controls participated in this study. Genotyping was performed by using polymerase chain reaction (PCR)-based methods. Genotype and allele distributions were significantly different between the schizophrenia patients and controls. In particular, the A2 allele was associated with an increased risk of schizophrenia (p = 0.003; odds ratio (OR) = 1.799; confidence interval (CI) = 1.192-2.716). However, the polymorphism was not different when the patient group was subdivided by the presence or absence of family history and by positive and negative subgroups according to the positive and negative syndrome scale (PANSS) score on schizophrenia. The results of this study replicated those of previous findings from Western countries and indicates the need for further studies on the potential role of the cPLA2 gene polymorphism in the susceptibility to schizophrenia.

This study is aimed to test the association between the coding sequence functional polymorphism (Ile105Val) of glutathione S-transferase P gene (GSTP1) and schizophrenia in the Korean population. Two hundred fourteen patients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria and 110 healthy controls were enrolled in this study. Patients and controls were biologically unrelated age and sex-matched native Koreans. Genotyping for GSTP1 polymorphism was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Genotype and allele distributions of GSTP1 polymorphism in patients with schizophrenia were not significantly different from those of the controls. Comparisons of clinical variables including Positive and Negative Syndrome Scale (PANSS), change of Brief Psychiatric Rating Scale (BPRS), number of admission, and onset age also were not different according to genotype distribution. The present study suggests that GSTP1 polymorphism may not confer susceptibility to development of schizophrenia in the Korean population.