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This study aimed to evaluate the psychometric properties of the Korean version of the Clinically Useful Anxiety Outcome Scale (CUXOS) and to examine the current diagnostic comorbidity and differential severity of anxiety symptoms between major depressive disorder (MDD) and anxiety disorders. In total, 838 psychiatric outpatients were analyzed at their intake appointment. Diagnostic characteristics were examined using the structured clinical interview from the DSM-IV because the DSM5 was not available at the start of the study. The CUXOS score was measured and compared with that of 3 clinician rating scales and 4 self-report scales. The CUXOS showed excellent results for internal consistency (Cronbach's α = 0.90), test-retest reliability (r = 0.74), and discriminant and convergent validity. The CUXOS significantly discriminated between different levels of anxiety severity, and the measure was sensitive to change after treatment. Approximately 45% of patients with MDD were additionally diagnosed with anxiety disorders while 55% of patients with anxiety disorders additionally reported an MDD. There was a significant difference in CUXOS scores between diagnostic categories (MDD only, anxiety only, both disorders, and no MDD or anxiety disorder). The CUXOS scores differed significantly between all categories of depression (major, minor, and non-depression) except for the comparison between minor depression and non-depression groups. The Korean version of the CUXOS is a reliable and valid measure of the severity of anxiety symptoms. The use of the CUXOS could broaden the understanding of coexisting and differentiating characteristics of anxiety and depression.

Vortioxetine was approved by the U.S. Food and Drug Administration (FDA) in September 2013 for treating major depressive disorder (MDD). Thus far, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with MDD. We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD. We performed an extensive search of databases and the clinical trial registry. The mean change in total scores on the 24-item Hamilton Rating Scale for Depression (HAM-D) and the Montgomery–Åsberg Depression Rating Scale (MADRS) from the baseline were the primary outcome measures. The secondary efficacy measures were the response and remission rates, as defined by a 50% or greater reduction in HAM-D/MADRS total scores and as a score of 10 or less in the MADRS and 7 or less in the HAM-D total scores at the end of treatment. We included 7 published and 5 unpublished short-term (6–12 wk) RCTs in our meta-analysis. Vortioxetine was significantly more effective than placebo, with an effect size (standardized mean difference [SMD]) of −0.217 (95% confidence interval [CI] −0.313 to −0.122) and with odds ratios (ORs) for response and remission of 1.652 (95% CI 1.321 to 2.067) and 1.399 (95% CI 1.104 to 1.773), respectively. Those treated with vortioxetine did not differ significantly from those treated with selective norepinephrine reuptake inhibitors/agomelatine with regard to the SMD of the primary outcome measure (0.081, −0.062 to 0.223) or for response (OR 0.815, 95% CI 0.585 to 1.135) and remission (OR 0.843, 95% CI 0.575 to 1.238) rates. Discontinuation owing to lack of efficacy (OR 0.541, 95% CI 0.308 to 0.950) was significantly less common among those treated with vortioxetine than among those who received placebo, whereas discontinuation owing to adverse events (AEs; OR 1.530, 95% CI 1.144 to 2.047) was significantly more common among those treated with vortioxetine than among those receiving placebo. There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957). Studies examining the role of vortioxetine in the treatment of MDD are limited. Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.

Background: We performed a meta-analysis in order to determine which neuropsychological domains and tasks would be most sensitive for discriminating between patients with major depressive disorder (MDD) and healthy controls. Methods: Relevant articles were identified through a literature search of the PubMed and Cochrane Library databases for the period between January 1997 and May 2011. A meta-analysis was conducted using the standardized means of individual cognitive tests in each domain. The heterogeneity was assessed, and subgroup analyses according to age and medication status were performed to explore the sources of heterogeneity. Results: A total of 22 trials involving 955 MDD patients and 7,664 healthy participants were selected for our meta-analysis. MDD patients showed significantly impaired results compared with healthy participants on the Digit Span and Continuous Performance Test in the attention domain; the Trail Making Test A (TMT-A) and the Digit Symbol Test in the processing speed domain; the Stroop Test, the Wisconsin Card Sorting Test, and Verbal Fluency in the executive function domain; and immediate verbal memory in the memory domain. The Finger Tapping Task, TMT-B, delayed verbal memory, and immediate and delayed visual memory failed to separate MDD patients from healthy controls. The results of subgroup analysis showed that performance of Verbal Fluency was significantly impaired in younger depressed patients (<60 years), and immediate visual memory was significantly reduced in depressed patients using antidepressants. Conclusions: Our findings have inevitable limitations arising from methodological issues inherent in the meta-analysis and we could not explain high heterogeneity between studies. Despite such limitations, current study has the strength of being the first meta-analysis which tried to specify cognitive function of depressed patients compared with healthy participants. And our findings may provide clinicians with further evidences that some cognitive tests in specific cognitive domains have sensitivity to discriminate MDD patients from healthy controls.

Major depressive disorder (MDD) is a chronic and recurrent mental condition leading to huge impacts on direct and indirect personal and public medical costs. To overcome such a serious mental disorder, we currently have a number of different classes of antidepressants, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, noradrenergic and specific serotonin receptor antagonists, dopamine and norepinephrine reuptake inhibitors, along with newly introduced antidepressants (e.g., vilazodone and agomelatine). However, a number of well-controlled clinical trials, meta-analyses and practical clinical studies have found that only a third of such MDD patients remit following adequate antidepressant treatment, while most MDD patients suffer from significant core depressive or residual symptoms during their clinical course. There have been some treatment approaches to overcome such a shortage of antidepressant efficacy, such as augmentation of psychotropics other than antidepressants, switching to a different antidepressant and combinations of different antidepressants. Among these different second treatment options, augmentation treatment has some favorable points compared with the combination and switching option (e.g., maintaining previous antidepressant partial response, synergistic effect between different pharmacological profile and no need to wash out previous antidepressants). Recently, second-generation antipsychotics (SGAs), olanzapine plus fluoxetine, quetiapine extended release and aripiprazole have clearly demonstrated efficacy in the treatment of MDD patients through a number of small-scale, open-label studies or randomized, placebo-controlled clinical trials. Eventually, in November 2007, aripiprazole was the first approved by the US FDA as an adjunctive treatment to antidepressants for treating MDD, followed by the approval of quetiapine and olanzapine plus fluoxetine at 2009. This comprehensive review provides an overview of the clinical trial data of SGAs for treating MDD and clinical issues raised in the use of SGA therapy in patients with MDD in clinical practice.

Background Mapping metabolic “signatures” can provide new insights into addictive mechanisms and potentially identify biomarkers and therapeutic targets. Objective We examined the differences in metabolites related to the tyrosine, tryptophan, purine, and oxidative stress pathways between cocaine-dependent subjects and healthy controls. Several of these metabolites serve as biological indices underlying the mechanisms of reinforcement, toxicity, and oxidative stress. Methods Metabolomic analysis was performed in 18 DSM-IV-diagnosed cocaine-dependent individuals with at least 2 weeks of abstinence and ten drug-free controls. Plasma concentrations of 37 known metabolites were analyzed and compared using a liquid chromatography electrochemical array platform. Multivariate analyses were used to study the relationship between severity of drug use [Addiction Severity Index (ASI) scores] and biological measures. Results Cocaine subjects showed significantly higher levels of n -methylserotonin ( p  < 0.0017) and guanine ( p  < 0.0031) and lower concentrations of hypoxanthine ( p  < 0.0002), anthranilate ( p  < 0.0024), and xanthine ( p  < 0.012), compared to controls. Multivariate analyses showed that a combination of n -methylserotonin and xanthine contributed to 73% of the variance in predicting the ASI scores ( p  < 0.0001). Logistic regression showed that a model combining n -methylserotonin, xanthine, xanthosine, and guanine differentiated cocaine and control groups with no overlap. Conclusions Alterations in the methylation processes in the serotonin pathways and purine metabolism seem to be associated with chronic exposure to cocaine. Given the preliminary nature and cross-sectional design of the study, the findings need to be confirmed in larger samples of cocaine-dependent subjects, preferably in a longitudinal design.

Background Genome-wide association studies (GWAS) represent the current frontier in pharmacogenomics. Thousands of subjects of Caucasian ancestry have been included in previous GWAS investigating antidepressant response. GWAS focused on this phenotype are lacking in Asian populations. Methods A sample of 109 major depressive disorder (MDD) patients of Korean origin in antidepressant treatment was collected. Phenotypes were response and remission according to the Hamilton Rating Scale for Depression (HRSD). Genome-wide genotyping was performed using the Illumina Human Omni2.5-8 platform. The same phenotypes were used in the STAR*D level 1 ( n  = 1677) for independent replication. In order to corroborate findings and increase the comparability between the two datasets, three levels of analysis (SNPs, genes and pathways) were carried out. Bonferroni correction, permutations, and replication across samples were used to reduce the risk of false positives. Results Among the genes replicated across the two samples (permutated p  < 0.05 in both of them), CTNNA3 appeared promising. The inorganic cation transmembrane transporter activity pathway (GO:0022890) was associated with antidepressant response in both samples ( p  = 2.9e-5 and p  = 0.001 in the Korean and STAR*D samples, respectively) and this pathway included CACNA1A , CACNA1C , and CACNB2 genes. Conclusions The present study supported the involvement of genes coding for subunits of L-type voltage-gated calcium channel in antidepressant efficacy across different ethnicities but replication of findings is required before any definitive statement.

Dependence on tobacco, like many other drug dependencies, is a complex behavior with both genetic and environmental factors contributing to the variance. The heritability estimates for smoking in twin studies have ranged from 46 to 84%, indicating a substantial genetic component to smoking. Candidate gene studies have detected functional polymorphisms in genes coding for the cytochrome P450 enzymes, and variations in these genes that lead to more rapid nicotine metabolism have been implicated in smoking. Similarly, smoking has been associated with polymorphisms in dopaminergic genes that may influence the dopamine receptor number and/or function. Animal experiments have localized specific subunits of the nicotinic receptors that may mediate the reinforcing properties of nicotine and have investigated their role in nicotine dependence. However, environmental factors have also been found to contribute to the risk of initiation and persistence of smoking. We review the scientific evidence that supports a role for genetic influences on smoking, discuss the specific genetic and neurobiological mechanisms that may mediate susceptibility to nicotine dependence, identify possible gene/environmental interactions that may be important in understanding smoking behavior, and suggest directions for future research. Insights into the genetic contributions to smoking can potentially lead to more effective strategies to reduce smoking.

Fatigue is one of the most common symptoms found in both community and medical care settings. Fatigue may imply a prodromal or residual symptom of major depressive disorder or an adverse reaction to antidepressant treatment. Fatigue may also compromise antidepressant treatment by delaying response to antidepressants. Despite the importance of fatigue as a core depressive symptom, data specific to the effects of fatigue on pharmacological treatment are still lacking. Bupropion is an atypical antidepressant, chemically unrelated to classical agents such as tricyclic antidepressants, selective serotonin reuptake inhibitors and other contemporary antidepressants. With a pharmacological profile that involves neurotransmitter reuptake inhibition, bupropion shares a broad range of biological properties with psychostimulants. The primary action mode of bupropion involves dopaminergic and noradrenergic neurotransmissions rather than serotonergic mechanisms, although its exact pharmacodynamic properties remain uncertain. Hence, it is possible that bupropion may play a role in the treatment of fatigue-related symptoms of major depressive disorder. This paper presents a brief overview of the clinical implications and neurobiology of major depressive disorder-related fatigue, as well as the pharmacological profile of bupropion and currently available clinical data related to its treatment of fatigue-related symptoms of major depressive disorder.

Improving medication adherence is critical to improving outcomes in patients with schizophrenia. A long-acting injectable (depot) antipsychotic is one of the most effective methods for improving treatment adherence and decreasing rehospitalization rates in patients with schizophrenia. Until recently, only three second-generation antipsychotics were available in a long-acting injectable formulation (risperidone, paliperidone, and olanzapine). In this respect, the emergence of long-acting aripiprazole injection (ALAI), approved by the US Food and Drug Administration for the treatment of schizophrenia in 2013, is timely. ALAI is a lyophilized powder of aripiprazole, and the aripiprazole molecule is unmodified. The initial and target dosage of ALAI is 400 mg once monthly, but it could be reduced to 300 mg if adverse reactions occur with 400 mg. When first administering ALAI, it is recommended to continue treatment with oral aripiprazole (10-20 mg/day) or another oral antipsychotic for 2 weeks in order to maintain therapeutic antipsychotic concentrations. The primary clearance route for ALAI is hepatic, ie, cytochrome P450 (CYP)2D6 and CYP3A4, so dose adjustment is required in poor CYP2D6 metabolizers. The efficacy of ALAI was demonstrated in three studies. A randomized controlled trial that formed the basis for approval of ALAI in the treatment of schizophrenia showed that ALAI significantly delayed time to impending relapse when compared with placebo (P<0.0001, log-rank test). An open-label, mirror study demonstrated that total psychiatric hospitalization rates were significantly lower after switching from oral antipsychotics to ALAI. Another randomized controlled trial presented in poster form suggested that ALAI 400 mg was comparable with oral aripiprazole 10-30 mg in preventing relapse. ALAI was generally well tolerated during both short-term and long-term studies. Its tolerability profile, including extrapyramidal symptoms and clinically relevant metabolic parameters, was similar to placebo. However, insomnia, headache, anxiety, akathisia, weight gain, injection site pain, and tremor need clinical attention. These studies suggest that ALAI is a viable treatment option for patients with schizophrenia, but direct head-to-head comparisons between ALAI and other long-acting injectable antipsychotics are needed to elucidate its risk-benefit profile.

There is a growing body of evidence that supports the use of atypical antipsychotics as augmentation agents for nonpsychotic unipolar major depressive disorder (MDD) in adults. Unfortunately, varying definitions of treatment-resistant depression, the limited evidence available for interventions after two or more treatment failures, and when and whether to use medications from nonantidepressant classes, remain a key gap in the knowledge base for clinicians. We identified and reviewed the following guidelines to discuss the status of augmentation therapy with atypical antipsychotic agents in MDD: American Psychiatric Association practice guidelines for treatment of patients with MDD; Canadian Network for Mood and Anxiety Treatments clinical guidelines for the management of MDD in adults; National Institute for Health and Clinical Excellence guidelines for treatment and management of depression in adults; British Association of Psychopharmacology guidelines for treatment of depressive disorders; Institute for Clinical Systems Improvement healthcare guideline for MDD in adults in primary care; clinical practice recommendations for depression; international consensus statement on MDD; German Society of Psychiatry, Psychotherapy and Neurology guidelines for unipolar depression; and World Federation of Societies of Biological Psychiatry guidelines for biological treatment of unipolar depressive disorders in primary care. Reflecting the cumulative evidence in the past decade, augmentation strategies including atypical antipsychotic augmentation are recommended in most guidelines for partial or nonresponders, at the same stage as switching or combination strategies. However, there are few direct comparisons of different augmentation strategies and little information about the optimal duration of augmentation strategies or use in special populations. Clinicians should note that guidelines are derived from an evolving database of evidence and cannot take into account the myriad of clinical variables that differ between individual patients. Therefore, they are intended to provide a useful framework for the management of depression and should be used in conjunction with other recognized sources of patient information and the application of clinical wisdom.