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Background Both Major Depressive Disorder (MDD) and Primary Insomnia (PI) have been linked to deficiencies in cortical γ-aminobutyric acid (GABA) and glutamate (Glu) thus suggesting a shared neurobiological link between these two conditions. The extent to which comorbid insomnia contributes to GABAergic or glutamatergic deficiencies in MDD remains unclear. Methods We used single-voxel proton magnetic resonance spectroscopy (1H MRS) at 4 Tesla to examine GABA+ and Glu relative to creatine (Cr) in the dorsal anterior cingulate cortex (dACC) and in the parieto-occipital cortex (POC) of 51 non-medicated adults with MDD, 24 adults with Primary Insomnia (PI), and 25 age- and sex-matched good sleeper controls (HC). Measures of depression severity and subjective and objective sleep quality were compared with 1H MRS metabolite measures. Results MDD subjects exhibited a 15% decrease in Glu/Cr in the dACC compared to HC. Within the MDD group, there was a trend inverse correlation between dACC Glu/Cr and anhedonia ratings. We observed no significant association between measures of sleep quality with dACC Glu/Cr in those with MDD. Limitations The protocol and data interpretation would have been enhanced by the recruitment of MDD subjects with a broader range of affect severity and a more comprehensive assessment of clinical features. Conclusions These findings support the role of cortical glutamatergic mechanisms in the pathophysiology of MDD. Insomnia severity did not further contribute to the relative deficiency of glutamatergic measures in MDD.

Background Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. Methods 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300 mg/day], aripiprazole [≤2.5 mg/day], or sertraline [≥150 mg/day]) were randomized to naltrexone 1 mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. Results All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN, from 30.7±4.3 to 22.8±8.5) for placebo (d=1.45; p=0.035). MADRS-15 item scores decreased from 36.6±6.2 to 13.2±8.8 for LDN, from 36.7±4.2 to 26.0±10.0 for placebo (d=1.49; p=0.035). Clinical Global Improvement Scale-Severity (CGI-S) scores decreased from 4.3±0.5 to 3.0±1.1 for LDN, from 4.3±0.5 to 4.0±0.6 for placebo (d=1.22; p=0.064). Limitations Small study; restrictions on allowed antidepressants. Conclusion LDN augmentation showed some benefit for MDD relapse on dopaminergic agents. Confirmation in larger studies is needed.

Previously, we found an anxiolytic effect of ziprasidone augmentation to escitalopram (compared with placebo augmentation) in patients with depression in an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial. Here, we carried out a post-hoc analysis, comparing changes in the Hamilton Depression and Anxiety Rating Scales between patients with anxious depression versus nonanxious depression, using a moderator analysis. Hamilton Depression Rating Scales total change scores from baseline and endpoint were not significantly different (interaction term P=0.91) in patients with anxious depression on ziprasidone augmentation (n=19; -9.1±4.9) or placebo (n=19; -6.1±8.9) versus patients without anxious depression on ziprasidone (n=52; -5.5±6.7) or placebo (n=49; -2.3±4.5). There was a trend toward statistical significance (interaction term P=0.1) in favor of patients without anxious depression for a difference in Hamilton Anxiety Rating Scale total change scores from baseline to endpoint [patients with anxious depression on ziprasidone augmentation (n=19; -2.7±5.3) or placebo (n=19; -3.3±5.8) versus patients without anxious depression on ziprasidone (n=51; -3.9±6.6) or placebo (n=44; -0.9±4.7)]. Ziprasidone augmentation was equally efficacious in treating depression in patients with versus without anxious depression. However, the observed anxiolytic effect for patients with higher anxiety was not clinically significant.

Scrupulosity is a subtype of obsessive-compulsive disorder (OCD) defined by religious or moral fears. Although the relationship between personality and OCD has been extensively studied, it remains unclear how personality relates specifically to religious obsessions and scrupulous fears. In the current study, we examined the association between scrupulosity and personality characteristics, including the Five Factor Model (FFM) and obsessive-compulsive personality disorder (OCPD), in a sample of individuals with self-reported obsessive-compulsive (OC) symptoms. Seventy-nine participants completed an anonymous online survey. FFM traits did not, but OCPD traits did, explain a significant amount of variance in scrupulosity. We also replicated previous findings showing that individuals with greater OC symptoms score lower on Extraversion and higher on Neuroticism. These findings suggest that scrupulous symptoms may not be specifically linked with any of the FFM personality factors, but may be associated with OC...

BACKGROUND: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. METHODS: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥ 3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS28-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. RESULTS: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P CONCLUSIONS: In this preliminary study, repeated doses of open-label ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01582945.© Copyright 2016 Physicians Postgraduate Press, Inc. Language: en

Background: Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone’s safety and efficacy as an augmentation agent in outpatients with partially remitted major depressive disorder (MDD) with residual symptoms of anger and irritability. Methods: A total of 13 outpatients with partially remitted MDD [currently treated with selective serotonin reuptake inhibitors (SSRIs)] received four weeks of iloperidone or placebo, followed by one week of washout. Patients were then crossed over to the other treatment arm for 4 weeks. Treatment arms were randomized and double blind; and two sites were used for the study. Analyses compared treatment response using the Symptom Questionnaire (SQ) Anger/Hostility Subscale as the primary outcome measure. Results: There was no significant differential effect of iloperidone × weeks on the SQ Anger/Hostility Subscore over the course of the study, compared with placebo × weeks, regardless of administration order ( p = 0.77). Conclusions: Iloperidone did not significantly outperform placebo on measures of anger or irritability in patients with partially remitted MDD and residual anger/irritability.

Background Despite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD. Methods Fifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging. Results Thirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state. Conclusions Gamma Knife ventral capsulotomy is an effective radiosurgical procedure for many treatment-refractory OCD patients. A minority of patients developed cysts at long-term follow-up, 1 of whom had permanent neurological sequelae.

Background Several studies indicate that ketamine has rapid antidepressant effects in patients with treatment-resistant depression (TRD). The extent to which repeated doses of ketamine (versus placebo) reduce depression in the short and long term among outpatients with TRD and chronic, current suicidal ideation remains unknown. Methods Twenty-six medicated outpatients with severe major depressive disorder with current, chronic suicidal ideation were randomized in a double-blind fashion to six ketamine infusions (0.5 mg/kg over 45 minutes) or saline placebo over three weeks. Depression and suicidal ideation were assessed at baseline, 240 min post-infusion, and during a three-month follow-up phase. Results During the infusion phase, there was no differences in depression severity or suicidal ideation between placebo and ketamine (p = 0.47 and p = 0.32, respectively). At the end of the infusion phase, two patients in the ketamine group and one in the placebo group met criteria for remission of depression. At three-month follow-up, two patients in each group met criteria for remission from depression. Limitations Limitations include the small sample size, uncontrolled outpatient medication regimens, and restriction to outpatients, which may have resulted in lower levels of suicidal ideation than would be seen in emergency or inpatient settings. Conclusions Repeated, non-escalating doses of ketamine did not outperform placebo in this double-blind, placebo controlled study of patients with severe TRD and current, chronic suicidal ideation. This result may support our previously published open-label data that, in this severely and chronically ill outpatient population, the commonly used dose of 0.5 mg/kg is not sufficient.

BACKGROUND Children whose parents have cancer are at risk for psychosocial difficulties; however, the mechanisms are not well understood. This cross-sectional study sought support for a model connecting parental cancer to child distress through its impact on parenting self-efficacy beliefs and parenting behaviors by examining relations among parental illness, quality of life/parent functioning, parenting efficacy beliefs, and concerns about children's emotional distress. METHODS One hundred ninety-four adult oncology outpatients with children who were 18 years old or younger completed questionnaires assessing their health-related quality of life (Functional Assessment of Cancer Therapy–General), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), overall distress (Distress Thermometer), and parenting efficacy beliefs and parenting concerns (Parenting Concerns Questionnaire). RESULTS Parenting efficacy scores for parents and coparents declined significantly after diagnosis. This decline correlated with more visits to a medical clinic, treatment with intravenous chemotherapy in the past month, poorer health-related quality of life, and more depression and distress. Parents experiencing the most concern about the impact of mood, physical limitations, and changes in routines on their children experienced the biggest declines in their own sense of efficacy as parents and in their belief in their coparent's efficacy. Finally, declines in parenting efficacy beliefs correlated with parental concerns about children's emotional distress about aspects of the parent's illness. CONCLUSIONS This study highlights the importance of identifying and addressing parenting concerns to alleviate patient distress, and it may help to guide future intervention efforts. Cancer 2015;121:3435–43. © 2015 American Cancer Society.

Despite their prevalence, depression and suicidal ideation (SI) are relatively unaddressed problems in the college student population. There are limited individual treatment studies targeting this population. Nine students (M = 19.33 years of age; SD ± .87) with depressive symptoms and/or SI were enrolled in 6-weeks of individual cognitive behavioral therapy (CBT) with a individually tailored manual-based treatment delivery. Measures were given before and after treatment. Primary results, presented as a case series, suggested decreases in depression across students and an overall downward trend in SI. As a secondary analysis, paired samples t tests showed significant decreases in both depression and SI. In summary, short-term, individually tailored manual-based CBT may be beneficial for reducing depressive symptoms and SI among college students. More research is needed to determine the best clinical interventions and targeted treatments for this vulnerable population.

We have previously shown an association between patient belief and treatment response in the Hypericum Depression Trial Study Group's 2002 study. We re-examined these data to determine whether clinical improvement was associated with physician belief about assigned therapy.Three hundred and forty adults with major depression and baseline scores ≥20 on the 17-item Hamilton Depression Scale (HDRS-17) were randomized to Hypericum 900-1500mg/day, sertraline 50-100mg/day, or placebo for 8 weeks. At week 8, physicians guessed their patients' treatment. We analyzed 277 subjects with at least one post-baseline visit and physician guess data. We examined association between guess and improvement in HDRS-17 and whether treatment assignment moderated the effect of belief on remission (final HDRS-17 score8).Patient and doctor guesses agreed at 53% for sertraline, 68% for Hypericum, and 52% for placebo (kappa=0.37). Doctors guessed placebo correctly (38%) more than sertraline (18%) or Hypericum (19%) (p=0.001). Adverse event scores were significantly greater among subjects for which the clinicians guessed Hypericum (p0.001) or sertraline (p=0.005) compared to placebo. Significant improvements in HDRS-17 score were found when comparing the Hypericum-guess (p0.001) or the sertraline-guess group (p0.001) against the placebo-guess group. Remission rates were significantly greater for subjects whose clinicians guessed sertraline (p0.001) or Hypericum (p0.001) versus placebo.Doctors tended to guess placebo more easily than Hypericum or sertraline, and their guesses tended to favor active therapies when improvement was more robust. Results show association but not causation, and merit more careful investigation.

Suicide is the third leading cause of death in college students, but there is limited consensual evidence to guide clinicians’ assessment and management of suicide. The aim of the current study was to assess the capability of a simple and practical measure, the Beck Depression Inventory (BDI) suicide item, to identify college students at high risk of suicide. Exploration of this research question could have important implications in this vulnerable population for identifying those at risk for suicide. Six-hundred-and-fifty-seven college students participated in a mental health screening and completed the BDI and the Suicidal Behaviors Questionnaire-Revised (SBQ-R), which is a detailed measure of suicide risk. We dichotomized the BDI suicide item, which measures suicidal ideation within the past week (presence vs. absence of suicidal ideation) as well as the SBQ-R total score (low vs. high risk of suicide). We computed the kappa statistic for the examination of agreement between these two measures. The kappa coefficient for the BDI suicide item and the SBQ-R was 0.57 for dichotomized scores. The BDI suicide item had a positive predictive value of 74 %, and a negative predictive value of 93 %. In a hierarchical linear regression, the BDI suicide item alone significantly predicted elevated scores on the SBQ-R [Chi square (1) = 128.427, p

Purpose National initiatives, such as the UK Improving Access to Psychological Therapies program (IAPT), demonstrate the feasibility of conducting empirical mental health assessments on a large scale, and similar initiatives exist in other countries. However, there is a lack of international consensus on which outcome domains are most salient to monitor treatment progress and how they should be measured. The aim of this project was to propose (1) an essential set of outcome domains relevant across countries and cultures, (2) a set of easily accessible patient-reported instruments, and (3) a psychometric approach to make scores from different instruments comparable. Methods Twenty-four experts, including ten health outcomes researchers, ten clinical experts from all continents, two patient advocates, and two ICHOM coordinators worked for seven months in a consensus building exercise to develop recommendations based on existing evidence using a structured consensus-driven modified Delphi technique. Results The group proposes to combine an assessment of potential outcome predictors at baseline (47 items: demographics, functional, clinical status, etc.), with repeated assessments of disease-specific symptoms during the treatment process (19 items: symptoms, side effects, etc.), and a comprehensive annual assessment of broader treatment outcomes (45 items: remission, absenteeism, etc.). Further, it is suggested reporting disease-specific symptoms for depression and anxiety on a standardized metric to increase comparability with other legacy instruments. All recommended instruments are provided online (www.ichom.org). Conclusion An international standard of health outcomes assessment has the potential to improve clinical decision making, enhance health care for the benefit of patients, and facilitate scientific knowledge. Electronic supplementary material The online version of this article (doi:10.1007/s11136-017-1659-5) contains supplementary material, which is available to authorized users.

In treated patients with major depressive disorder (MDD), residual symptoms are common and challenging to disentangle from possible antidepressant side effects. Our objective was to prospectively differentiate between rates of residual symptoms and treatment-emergent side effects.Participants in an episode of MDD were enrolled in a 6-week trial of an antidepressant. Assessments occurred at baseline and after 6 weeks of treatment, using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ). Among treatment responders, residual symptoms were those that remained the same or improved. Side effects were defined as newly emergent or worsening symptoms.Of 403 participants, 284 completed (70.5%) the trial; 93 (32.7%) were treatment responders. Residual symptoms were common and represented a substantially greater burden than side effects at end point. This was true across symptoms of depression broadly, as captured by items with the QIDS-SR and the MGH CPFQ.Prospective assessment is crucial to discriminate between residual symptoms and side effects during antidepressant treatment. This study demonstrated that after 6 weeks of active treatment, symptoms are likely to persist despite response to treatment and are much less likely to represent side effects of medication treatment.

Background Failed treatment trials are common in major depressive disorder and treatment-resistant depression, and remotely performed multifaceted, centralized structured interviews can potentially enhance signal detection by ensuring that enrolled patients meet eligibility criteria. Methods We assessed the use of a specific remote structured interview that validated the diagnosis, level of treatment resistance, and depression severity. The objectives were to (1) assess the rate at which patients who were deemed eligible for participation in trials by site investigators were ineligible, (2) assess the reasons for ineligibility, (3) compare rates of ineligibility between academic and nonacademic sites, (4) compare eligibility between US and non-US sites, and (5) report the placebo response rates in trials utilizing this quality assurance approach, comparing its placebo response rates with those reported in the literature. Methods included a pooled analysis of 9 studies that utilized this methodology (SAFER interviews). Results Overall, 15.33% of patients who had been deemed eligible at research sites were not eligible after the structured interviews. The most common reason was that patients did not meet the study requirements for level of treatment resistance. Pass rates were significantly higher at non-US compared with US sites (94.6% vs 83.3%, respectively; P < 0.001). There was not a significant difference between academic and nonacademic sites (87.8% vs 82.4%; P = 0.08). Placebo response rates were 13.0% to 27.3%, below the 30% to 40% average in antidepressant clinical trials, suggesting a benefit of the quality assurance provided by these interviews. Conclusions The use of a remotely structured interview by experienced clinical researchers was feasible and possibly contributed to lower-than-average placebo response rates. The difference between US and non-US sites should be the subject of further research.

The aim of this study was to evaluate efficacy of ziprasidone monotherapy for major depressive disorder (MDD) with and without psychomotor symptoms. In accordance with the sequential parallel comparison design, 106 MDD patients (age 44.0±10.7 years; female, 43.4%) were recruited and a post-hoc analysis was carried out on 12-week double-blind treatment with either ziprasidone (40-160 mg/day) or placebo, divided into two phases of 6 weeks each to the assigned treatment sequences, drug/drug, placebo/placebo, and placebo/drug. Psychomotor symptoms were evaluated on the basis of the Mini-International Neuropsychiatric Interview at baseline. Efficacy assessments, on the basis of the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Quick Inventory of Depressive Symptomatology Scale, Self-Rated (QIDS-SR), were performed every week throughout the trial. In phase I, ziprasidone monotherapy produced significant improvement in patients with psychomotor symptoms compared with placebo on the basis of HDRS-17 (F=5.95, P=0.017) and QIDS-SR (F=5.26, P=0.025) scores, whereas no significant changes were found in HDRS-17 (F=2.32, P=0.15) and QIDS-SR (F=3.70, P=0.074) scores in patients without psychomotor symptoms. In phase II, ziprasidone monotherapy produced no significant differences compared with placebo. In the pooled analysis, ziprasidone monotherapy showed significance according to QIDS-SR (Z=2.00, P=0.046) and a trend toward statistical significance according to the HDRS-17 (Z=1.66, P=0.10) in patients with psychomotor symptoms. Ziprasidone monotherapy may produce significant improvement compared with placebo in MDD patients with psychomotor symptoms.

Previous epidemiologic studies have revealed that East-Asian populations experience fewer depressive symptoms than American populations do. However, it is unclear whether this difference applies to clinical patients with major depressive disorder (MDD). This present study included 1592 Korean and 3744 American outpatients who were 18 years of age or older and met the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. criteria for single or recurrent episodes of nonpsychotic MDD, and evaluated their symptoms of depression using the Hamilton Depression Rating Scale and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form. Korean patients scored significantly lower for guilt and depressed mood items, and higher for hypochondriasis and suicidality items than American patients did, after adjusting for total Hamilton Depression Rating Scale scores. Conversely, no significant differences were found in quality and function of daily life between groups. Multivariate logistic regression analyses revealed that Korean patients experienced less frequent depressed mood and guilt, including verbal and nonverbal expression of depressed mood [adjusted odds ratio (AOR) = 0.14, 95% confidence interval (CI) 0.08-0.23] and feelings of punishment (AOR = 0.036, 95% CI 0.025-0.054) when compared with Americans after adjusting for age and sex. Conversely, Korean patients experienced more frequent suicidality and hypochondriasis, including suicidal ideas or gestures (AOR = 2.10, 95% CI 1.60-2.76) and self-absorption of hypochondriasis (AOR = 1.94, 95% CI 1.70-2.20). In conclusion, decreased expression of depressed mood and guilt may cause underdiagnosis of MDD in Korean patients. Early diagnosis of and intervention for depression and suicide may be delayed because of this specific cross-cultural difference in depression symptoms.

To compare outcomes from two different treatment strategies in Latino patients with major depressive disorder (MDD) and psychosis-like symptoms: antidepressant medications alone versus a combination of antipsychotic and antidepressant medications, we retrospectively examined the clinical charts of 37 Latino patients with MDD and psychosis-like symptoms from one of our community affiliated clinics, admitted from January 2010 to June 2011. Outcomes included depressive response and remission based on improvement in Patient Health Questionnaire-9 scores. Psychosis-like symptoms were assessed through a specific database created for the study. To qualify for outcomes analysis, patients had to have had adequate treatment with relevant medications for at least eight weeks at therapeutic doses. In all, 24 subjects met the criteria for analysis, and 11 received an antipsychotic medication. Of the 10 subjects who received an antipsychotic, 3 (30%) achieved depressive response. Of the 14 subjects who did not receive ...

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Randomized clinical trials in many conditions such as mental illness, pain, addiction, allergy and asthma are subject to moderate-to-high rates of placebo response. This reduces the effect size for the comparison of the active treatment to the placebo group, hence reducing the efficiency of studies. Since attempts to resolve this problem using a placebo lead-in design have not been successful, in 2003 the sequential parallel comparison design (SPCD) was developed. In the SPCD, the study is conducted in two treatment stages, with the efficacy analysis including (a) all subjects in stage 1 and (b) stage 2 data from stage 1 placebo nonresponders. The relevant data from the two stages are pooled to compute an overall p-value. This article reviews the situations in which the SPCD is preferable to the standard parallel design as well as the circumstances in which SPCD is not a good choice.

Given the increasing interest in demonstrating effectiveness in psychiatric treatment, the current paper seeks to advance outcome measurement in child psychiatry by demonstrating how more informative analytic strategies can be used to evaluate treatment in a real world setting using a brief, standardized parent-report measure. Questionnaires were obtained at intake for 1294 patients. Of these, 695 patients entered treatment and 531 (74%) had complete forms at intake and follow-up. Using this sample, we analyzed the data to determine effect sizes, rates of reliable improvement and deterioration, and rates of clinically significant improvement. Findings highlighted the utility of these approaches for evaluating treatment outcomes. Further suggestions for improving outcome measurement and evaluation are provided.

Background Anxious depression, defined as MDD with high levels of anxiety symptoms, has been associated with lower rates of antidepressant response and remission as well as greater chronicity, suicidality and antidepressant side-effect burden. The primary aim of this study was to assess the effectiveness of cognitive therapy (CT) alone or in combination with medications for anxious versus non-anxious depression. Methods We assessed the STAR⁎D study participants who were partial or non-responders to citalopram. Subjects were then either switched (n=696) to a new antidepressant or to CT alone, or they were kept on citalopram and augmented (n=577) with another antidepressant or CT. We compared response and remission rates, across treatment conditions, between those who met criteria for anxious depression and those who did not. Results Those with anxious depression had significantly lower remission rates based on the QIDS, whether assigned to switch or augmentation, compared to those with non-anxious depression. Those with anxious depression, compared to those without, had significantly lower response rates based on the QIDS only in the switch group. There was no significant interaction between anxious depression and treatment assignment. Limitations Limitations include the use of citalopram as the only Level 1 pharmacotherapy and medication augmentation option, the relatively small size of the CT arms, use of depression-focused CT rather than anxiety-focused CT, and focus on acute treatment outcomes. Conclusions Individuals with anxious depression appear to experience higher risk of poorer outcome following pharmacotherapy and/or CT after an initial course of citalopram and continued efforts to target this challenging form of depression are needed.

We sought to examine the efficacy and safety of acamprosate augmentation of escitalopram in patients with concurrent major depressive disorder (MDD) and alcohol use disorders. Twenty-three adults (43% female; mean ± SD age, 46 ± 14 years) were enrolled and received 12 weeks of treatment with psychosocial support; escitalopram, 10 to 30 mg/d; and either acamprosate, 2000 mg/d (n = 12), or identical placebo (n = 11). Outcomes included change in clinician ratings of depressive symptoms, MDD response and remission rates, changes in frequency and intensity of alcohol use, retention rates, and adverse events. Twelve subjects (acamprosate, n = 7; placebo, n = 5) completed the study. There was significant mean reduction in ratings of depressive symptoms from baseline in both treatment arms (P < 0.05), with no significant difference between the groups. Those in the acamprosate group had a 50% MDD response rate and a 42% remission rate, whereas those in the placebo arm had a 36% response and remission rate (not significant). Those assigned to acamprosate had significant reduction in number of drinks per week and drinks per month during the trial, whereas those assigned to placebo demonstrated no significant change in any alcohol use parameter, but the between-group difference was not significant. There were no significant associations between change in depressive symptoms and change in alcohol use. Attrition rates did not differ significantly between the 2 arms. Acamprosate added to escitalopram in adults with MDD and alcohol use disorders was associated with reduction in the frequency of alcohol use. The present study was not powered to detect superiority versus placebo. Further study in a larger sample is warranted.

Purpose Young adults with ADHD have been shown to be at increased risk for impairment in driving behaviors. Although stimulant medications have proven efficacy in reducing ADHD symptomatology, there is limited knowledge as to their effects on driving behavior. The focus of this report is on assessing the impact of lisdexamfetamine dimesylate (LDX) on driving behaviors in young adults with ADHD using a validated driving behavior questionnaire. Methods This assessment was carried out in the context of a randomized, double-blind, 6-week, placebo-controlled, parallel-design study of LDX versus placebo. Subjects were 61 outpatients of both sexes, 18–26 years of age, who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects were randomized to receive LDX or placebo for 6 weeks. Driving behavior was assessed at baseline and at the end of treatment using a U.S. version of the Manchester Driving Behavior Questionnaire (DBQ). Results Highly significant improvements were documented on LDX, over placebo, in driving behaviors assessed through the DBQ in measures of driving errors, driving lapses, and a trend toward fewer driving violations. There were no meaningful associations between these DBQ results and previously documented changes in a laboratory driving simulation paradigm or with improvement in symptoms of ADHD assessed through the ADHD rating scale. Conclusions LDX treatment was associated with significant improvements in self-reported driving behaviors that were independent of improvement in symptoms of ADHD. These results suggest that LDX may reduce behaviors associated with driving risks in young adults with ADHD.

Objective This pilot, randomized clinical trial investigates the effectiveness of tai chi as the primary treatment for Chinese Americans with major depressive disorder (MDD). Methods 67 Chinese Americans with DSM-IV MDD and no treatment for depression were recruited between March 2012 and April 2013 and randomized (1:1:1) into a tai chi intervention, an education program, or a waitlisted group for 12 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇); positive response for this outcome was defined as a decrease in total score of 50% or more, and remission was defined as HDRS₁₇ ≤ 7. Results Participants (N = 67) were 72% female with a mean age of 54 ± 13 years. No serious adverse events were reported. After the end of the 12-week intervention, response rates were 25%, 21%, and 56%, and remission rates were 10%, 21%, and 50% for the waitlisted, education, and tai chi intervention groups, respectively. The tai chi group showed improved treatment response when compared to both the waitlisted group (odds ratio [OR] = 2.11; 95% CI, 1.01-4.46) and to the education group (OR = 8.90; 95% CI, 1.17-67.70). Tai chi intervention showed significantly improved remission rate over the waitlisted group (OR = 3.01; 95% CI, 1.25-7.10), and a trend of improved remission compared to the education group (OR = 4.40; 95% CI, 0.78-24.17). Conclusions As the primary treatment, tai chi improved treatment outcomes for Chinese Americans with MDD over both passive and active control groups. Trial registration ClinicalTrials.gov identifier: NCT01619631.

Background Despite the availability of effective treatments for depression, many patients under the care of primary care physicians do not achieve remission. Clinical Outcomes in Measurement-based Treatment (COMET) was designed to assess whether communicating patient-reported depression symptom severity to primary care physicians affects patient outcomes at 6 months. Methods Nine hundred fifteen patients (intervention: n = 503; control: n = 412) diagnosed with major depressive disorder were enrolled in a prospective trial in which physician practice sites were assigned to either the intervention or control study arm. Only patients who were prescribed an antidepressant by their physician were eligible, but medication type was independent of the study protocol. Intervention-arm physicians received monthly updates on their patients’ depression severity, which was determined with the nine-item Patient Health Questionnaire (PHQ-9) administered during telephone interviews. Remission was defined as a PHQ-9 score

A 2-phase, mixed methods study was conducted to develop a Parenting Concerns Questionnaire (PCQ) for adults with cancer. Limited information about this area of psychosocial distress highlights the need for a measurement tool that can identify adult oncology patients with heightened parenting concerns who could benefit from additional intervention.Telephone focus groups were conducted with 16 oncology patients who had children 18 years old and younger. Group interview transcripts were analyzed to generate qualitative themes and candidate items for the PCQ. A 38-item version of the questionnaire was completed by 173 oncology outpatients who had children 18 years old and under. Participants also completed the Distress Thermometer, HADS (Hospital Anxiety and Depression Scale), and FACT-G (Functional Assessment of Cancer Therapy-General). Exploratory factor analyses revealed the emergence of 3 subscales of 5 items each, yielding a 15-item questionnaire. Associations between total PCQ scores, standardized measures of distress, depression, anxiety, quality of life, and demographic and illness characteristics were examined.The 15-item PCQ demonstrates good internal consistency (Cronbach's α = .83). PCQ scores were significantly associated (P.01) with standardized measures of psychosocial distress (Distress Thermometer, HADS, and FACT-G) in the expected directions. Higher PCQ scores were associated with female sex, single parenthood, metastatic or recurrent cancer, subjective understanding of incurable disease, comorbid chronic health condition, and current mental health treatment.The PCQ proved a reliable and valid measure of parenting distress among cancer patients, and thus merits further study.

Aim: We sought to determine whether weight and body mass index measurement were taken into consideration when prescribing second-generation antipsychotic (SGA) medication to a child. Methods: Two hundred clinicians were surveyed using a hypothetical clinical case vignette at a child psychopharmacology, postgraduate medical education course. The vignette described an overweight 10-year-old boy who was about to be prescribed an SGA medication to control psychotic symptoms. The reference to the patient's being ‘overweight’ was purposefully included to determine if providers would assess the patient's risk of morbidity from the metabolic side effects of the SGAs at the time of prescribing. Results: Only 7.0% of prescribers listed either ‘body mass index’ or a combination of ‘height’ and ‘weight’ as part of their next treatment steps for an overweight child before prescribing an SGA. Conclusions: These results suggest the need for education as to the importance of body mass index monitoring when prescribing second-generation antipsychotic medications to children.

Objectives: Scrupulosity is a relatively common but understudied subtype of obsessive-compulsive disorder (OCD) characterized by religious or moral fears. It is difficult to treat and frequently disabling. We examined scrupulosity as it relates to (a) treatment-seeking behavior and perceived treatment gains, (b) the perceived effect of symptoms on religious experience, and (c) conceptions of God. Method: Seventy-two individuals with scrupulous OCD (mean age = 36; 70% women) and 75 individuals with nonscrupulous OCD (mean age = 38; 81% women) completed an internet-based survey. Results: The groups did not differ on demographic variables or overall OCD severity. Compared with the nonscrupulous group, the scrupulous group was (a) more religious, (b) more likely to seek pastoral counseling, (c) less likely to seek medication treatment, and (d) more likely to report that symptoms interfered with their religious experience. Indeed, most scrupulous individuals endorsed that their symptoms interfered with their religious experience. Scrupulous individuals with a more negative concept of God experienced more severe symptoms, whereas a positive description of God was unrelated to severity of scrupulosity in this group. Nearly one in five scrupulous participants reported no religious affiliation. Conclusions: Scrupulous individuals have unique treatment-seeking preferences. Moreover, most scrupulous individuals perceive their symptoms as interfering with their religious experience. Focusing on the religious costs and benefits of scrupulous rituals might have clinical utility. Finally, scrupulous individuals with a more negative concept of God experienced more severe symptoms. Future research is necessary to evaluate whether addressing such concepts can improve treatment outcome. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–9, 2011.

OBJECTIVE To reanalyze data from a 2002 study by the Hypericum Depression Trial Study Group to determine whether patients who believed they were receiving active therapy rather than placebo obtained greater improvement, independent of treatment. METHOD Three hundred forty adults with major depressive disorder (according to the Structured Clinical Interview for DSM-IV) and baseline scores of ≥ 20 on the 17-item Hamilton Depression Rating Scale (HDRS-17) were randomized to Hypericum perforatum 900-1,500 mg/d, sertraline 50-100 mg/d, or placebo and were asked to guess their assigned treatment after 8 weeks. This reanalysis of data was performed from October 1, 2009, to April 15, 2011. The intent-to-treat sample included 207 subjects (mean age = 44 years) who had (1) at least 1 postbaseline visit; (2) adherence data based on serum levels of hyperforin, sertraline, and desmethylsertraline; and (3) guess data. Univariate factorial analysis of variance was used to determine whether treatment assignment affected clinical improvement according to HDRS-17 score and whether this effect was moderated by patient guess of sertraline, Hypericum, or placebo. Analysis of covariance was used to determine whether side effects mediated improvement in the context of patient guess and assigned treatment. χ₂ analyses compared response rates (≥ 50% decrease in HDRS-17 score) between the guess groups and between the treatment groups within each guess group. RESULTS Assigned treatment had no significant effect on clinical improvement (P = .65), but patient guess was significantly associated with improvement (P < .001), and treatment and guess interacted significantly (P = .005). Among subjects who guessed placebo, clinical improvement was small and did not differ significantly across treatments. Among subjects who guessed Hypericum, improvement was large and did not differ significantly across treatments. Among subjects who guessed sertraline, those who received placebo or sertraline had large improvements, but those who received Hypericum had significantly less improvement (P < .001). Similar findings were obtained for response rates. CONCLUSIONS Patient beliefs regarding treatment may have a stronger association with clinical outcome than the actual medication received, and the strength of this association may depend upon the particular combination of treatment guessed and treatment received.

Medical specialties, including surgery, obstetrics, anesthesia, critical care, and trauma, have adopted simulation technology for measuring clinical competency as a routine part of their residency training programs; yet, simulation technologies have rarely been adapted or used for psychiatry training. The authors describe the development of a web-based computer simulation tool intended to assess physician competence in obtaining informed consent before prescribing antipsychotic medication to a simulated patient with symptoms of psychosis. Eighteen residents participated in a pilot study of the Computer Simulation Assessment Tool (CSAT). Outcome measures included physician performance on required elements, pre- and post-test measures of physician confidence in obtaining informed consent, and levels of system usability. Data suggested that the CSAT increased physician confidence in obtaining informed consent and that it was easy to use. The CSAT was an effective educational tool in simulating patient—physician interactions, and it may serve as a model for use of other web-based simulations to augment traditional teaching methods in residency education.

OBJECTIVE This study sought to investigate the likelihood that subjects will respond to continued antidepressant therapy when little or no benefit has yet been observed. METHOD Six hundred twenty-seven subjects diagnosed with DSM-IV major depressive disorder were recruited in a 12-week open-label trial with fluoxetine, which was designed as a preliminary phase to a subsequent 52-week continuation trial, which was conducted in 1997-2003. For each week of the study, a calculation was made for all subjects who had heretofore demonstrated little or no improvement as to the likelihood of converting to a positive response in subsequent weeks as measured by the Clinical Global Impressions scale, the primary outcome measure. In order to compare our findings with prior research, we focused primarily on outcomes at weeks 6, 8, and 12. RESULTS The likelihood of converting to a positive response decreased the longer subjects remained unimproved. When week 6 was used as the end point, the likelihood of converting to a positive response for unimproved subjects at week 1 was 36% (n = 302); the respective conversion rates for weeks 2-5 were 29% (n = 208) at week 2, 18% (n = 151) at week 3, 17% (n = 120) at week 4, and 9% (n = 91) at week 5. When week 8 was used as the end point, the likelihood of converting to a positive response for unimproved subjects at week 4 was 23% (n = 118) and, at week 6, was 10% (n = 61). Finally, when week 12 was used as the end point, the likelihood of unimproved subjects at weeks 4, 6, and 8 converting to a positive response at week 12 was 50% (n = 117), 33% (n = 60), and 30% (n = 46), respectively. CONCLUSIONS The study adds to a small, but growing literature that gives clinicians some guidelines to help decide whether to continue an antidepressant trial when little or no benefit has yet been observed. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00427128.

Previous findings suggested a unique role that depression symptoms might play in the comorbid relationship between obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). However, the nature of this role remains unclear. Thus, the current study examined ways in which OCD and PTSD symptoms vary as a function of depression, as well as the mediating role of depression in the OCD-PTSD relationship, in 104 individuals seeking treatment for refractory OCD. Findings revealed that depressed individuals in the treatment-refractory OCD sample report higher levels of overall obsessing and greater severity of PTSD. In addition, depression appeared to mediate the relation between OCD and PTSD. Implications of findings are discussed.

Objective We test the hypothesis that racial or ethnic differences exist in relapse rates to fluoxetine discontinuation in major depressive disorder (MDD). Method Data are from a prospective study examining the relapse rates secondary to fluoxetine discontinuation in MDD. Subjects in the discontinuation phase consisted of 255 adults aged 18 to 65: 214 subjects who self-identified as white, 22 as African American, 13 as Latino American, and 6 as Asian American. Results In both the fluoxetine and placebo groups, no statistically significant differences emerged when comparing time to relapse for minority groups as compared to the white population. Adjusting for statistically significant predictors of relapse (symptom severity, neurovegetative symptom pattern, sex) and for educational level did not change the outcome of the survival analyses. Conclusions Although the size of minority groups in this sample was modest, in a randomized, controlled trial setting, minority and white patients may have similar rates of relapse in MDD. This finding reinforces the importance of maintenance treatment in relapse for both minority as well as white patients with MDD. Given the self-selecting nature of clinical trials, future studies are needed to further examine the potential influence of underlying cultural factors on clinical outcomes in minority populations.

The association between heavy alcohol consumption and risky behaviors has been amply investigated among college students. However, less is known with regard to types of drinking behaviors associated with high-risk activities. The present study extends this area of research by examining the relationship between compulsive drinking and hazardous behaviors in this population. Nine hundred and four college students completed measures on compulsive drinking and other risky behaviors in the context of mental health screenings at three campuses. Results showed that in males, compulsive drinking increased the risk for compulsive street drugs use, compulsive prescription drugs use, compulsive sexual activities, and gambling. Among females, compulsive drinking increased the risk for compulsive street drugs use, and compulsive sexual activities. These findings suggest that inquiring about compulsive drinking among college students may have great utility in identifying those at greater risk for other risky behaviors. The high co-occurrence of compulsive drinking, illicit substances, compulsive sexual activities, and gambling in college students suggests the need for comprehensive programs addressing high-risk behaviors together. (Am J Addict 2010;00:1-7). Language: en

Objective/Introduction: We sought to characterize the impact of the 90-item Symptom Checklist (SCL-90) subscales for paranoid ideation (PI) and psychoticism (P) in patients with major depressive disorder (MDD), on acute anti-depressant response and on relapse prevention.Methods: Subjects with Structured Clinical Interview for DSM Disorders-diagnosed non-psychotic MDD were recruited into a clinical trial of open-label fluoxetine 10–60 mg/day for 12 weeks, followed by double-blind randomization of responders (n=262) to fluoxetine continuation or placebo for 12 months. PI and P were assessed with the patient-rated SCL-90. The association of these symptoms with response to treatment was assessed by logistic regression.Results: We found significant decreases in PI and P during acute treatment phase for fluoxetine responders and nonresponders, although only 10.3% and 7.5% of patients experienced a ≥50% reduction in PI and P scores, respectively. Neither PI nor P scores significantly predicted time to relapse. P scores predicted a lower response rate to treatment with fluoxetine.Discussion: The results of the present study suggest that there is a significant relationship between the presence of psychoticism in patients with nonpsychotic MDD, and the likelihood of overall depressive symptom improvement following a trial of monotherapy with fluoxetine.Conclusion: An increased burden of psychoticism in depressed subjects may confer poorer response to fluoxetine, but not increased risk of relapse among fluoxetine responders.

The objective of this study was to assess the relationship between early changes in anxiety/somatization symptoms and treatment outcome among major depressive disorder patients during a 12-week trial of fluoxetine. We also examined the relationship between anxious depression and treatment response. Five hundred and ten major depressive disorder patients received 12 weeks of fluoxetine with flexible dosing [target dosages: 10 mg/day (week 1), 20 mg/day (weeks 2-4), 40 mg/day (weeks 4-8), and 60 mg/day (weeks 5-12)]. We assessed the relationship between early changes in 17-item Hamilton Rating Scale for Depression (HAMD-17)-anxiety/somatization factor items and depressive remission, as well as whether anxious depression at baseline predicted remission at study endpoint. Baseline HAMD-17 scores were considered as covariates and the Bonferroni correction (P < or = 0.008) was used for multiple comparisons. Adjusting for baseline HAMD-17 scores, patients who experienced greater early improvement in somatic symptoms (gastrointestinal) were significantly more likely to attain remission (HAMD-17

This research examined the potential relationship between adolescent problem behaviors and amount of time spent with violent electronic games. Survey data were collected from 1,254 7th and 8th grade students in two states. A “dose” of exposure to Mature-rated games was calculated using Entertainment Software Rating Board ratings of titles children reported playing “a lot in the past six months,” and average days per week of video game play. Analyses were conducted using simultaneous logistic regression for binary outcome variables, and simultaneous multiple linear regression for continuous outcome variables, controlling for a series of potential confounders. M-rated game dose predicted greater risk for bullying (p

Relapse of major depressive disorder (MDD) is a common clinical problem. Identifying relapse predictors could lead to strategies that reduce relapse risk. This study is designed to determine whether residual symptoms predict relapse risk during the continuation/maintenance treatment of MDD. 570 MDD patients received open-label fluoxetine for 12 weeks. Under double blind conditions, 262 patients who responded by week 12 were randomly assigned to continue fluoxetine or switch to placebo for 52 weeks or until relapse. Residual symptoms were measured using the Symptom Checklist-90 and the Symptom Questionnaire. The relationship between residual symptom severity and relapse risk was assessed. Without adjusting for overall residual symptom severity, a greater severity of residual obsessive-compulsive and phobic anxiety symptoms predicted greater relapse risk. After adjusting for overall residual symptom severity, only severity of phobic anxiety symptoms predicted relapse risk. The predictive value of phobic anxiety symptoms with respect to relapse risk was independent of treatment assignment. The results indicated that there may be a specific pattern of residual symptoms associated with depressive relapse during antidepressant continuation/maintenance, which is unrelated to treatment assignment. Future studies are needed to further explore the relationship between residual symptoms and relapse risk in MDD. Clinical implications: (1) It is important to treat residual symptoms among antidepressant responders/remitters in order to decrease relapse risk. (2) Clinicians should target residual phobic anxiety symptoms in order to decrease relapse risk. (3) Clinicians should target residual obsessive-compulsive symptoms in order to decrease relapse risk. Limitations: (1) limited generalizability due to inclusion/exclusion criteria; (2) lack of active comparator treatment group; (3) post hoc analysis.

Context: Evidence that the quality of medical care is improved by adverse event reporting is growing, but systemic improvement in patient safety remains uncoordinated and is driven by organizations and states, rather than by any unified plan. Massachusetts requires hospitals to report several types of major incidents to two different agencies, one set of reports are available to the public, the other kept strictly confidential. We analyzed the effect of the confidential reporting and feedback system on the number of reports, their type and whether they contained corrective actions, before and after a letter notifying hospitals of their failure to comply with the reporting statutes was sent in August 2003. This notification clearly held hospitals accountable for improved patient safety. Objective: To assess the changes in the number of reports filed for major incidents and the presence in the reports of corrective actions planned by the hospitals for the year before and two years after the compliance was sent. Design, Setting and Participants: All 1,317 major incident reports (MIRs) submitted in fiscal years 2003, 2004 and 2005 to the Patient Care Assessment Division (PCA) of the Board of Registration in Medicine of Massachusetts from all 94 acute care hospitals in Massachusetts were analyzed, including the presence of corrective actions included in their report to the PCA. MIRs were grouped by fiscal year, because the compliance letter holding hospitals accountable for improved patient safety was sent in FY 2003; thus improvements were expected to be seen from the baseline period of FY 2003, to the two subsequent fiscal years. Main Outcome Measures: Changes in number of reports of serious major incident reports and presence of hospitals' corrective actions included in reports. Results: Immediately following the baseline fiscal year of 2003, there was a large and significant increase in both the number of hospitals submitting at least one report and the mean number of reports submitted per hospital, and both numbers remained at this higher level in the third year. There was a significant increase in reports for fatal/life-threatening incidents as measured by the presence of corrective actions submitted by the hospitals in their reports, but this improvement lagged one year behind the increase in number of reports. Conclusions: The purpose of a mandatory adverse reporting system, holding hospitals accountable for improved patient safety and quality, is demonstrated by significant improvements in reporting compliance and the presence of corrective actions to the PCA during the three-year period examined.

Although personality disorder (PD) comorbidity has been associated with poor treatment outcome in major depressive disorder (MDD), little is known about mechanisms mediating this link. Converging evidence suggests that maladaptive cognitive patterns, particularly in interaction with stressors, might lead to poor treatment outcome in MDD subjects with PD pathology. The goal of this study was to test the role of PD comorbidity, cognitive vulnerability, and perceived stress in treatment outcome in MDD. Three hundred eighty-four MDD outpatients were enrolled in an 8-week open-label treatment of fluoxetine. Structural equation modeling and path analyses revealed that the effect of PD vulnerability on treatment outcome was fully mediated by increased pretreatment cognitive vulnerability and depression severity, which led to increased stress perception after treatment and poorer antidepressant response. Depressogenic cognitions might be continuously activated by chronic distress in MDD subjects reporting axis II pathology, leading to stress exacerbation and eventually poorer treatment outcome.

Objective To examine motoric, cardiovascular, endocrine, and metabolic effects of adjunctive ziprasidone in adults with major depressive disorder (MDD) and prior nonresponse to 8 weeks of open-label escitalopram. Methods A multicenter, parallel, randomized, double-blind, placebo-controlled trial was conducted at 3 US academic medical centers from July 2008 to October 2013. Recruited were 139 outpatients with persistent DSM-IV MDD following an 8-week open-label trial of escitalopram. Subjects were then randomized to adjunctive ziprasidone (escitalopram + ziprasidone, n = 71) or placebo (escitalopram + placebo, n = 68) for 8 additional weeks. Cardiac and metabolic measures were obtained at each treatment visit. Barnes Akathisia Scale and Abnormal Involuntary Movement Scale (AIMS) scores were also obtained. Changes in outcome measures for each treatment group were compared by independent-samples t test. Results A trend toward significance (P = .06) in corrected QT interval (QTc) increase was observed for ziprasidone (mean [SD] = 8.8 [20.2] milliseconds) versus placebo (-0.02 [25.5] milliseconds). Ziprasidone-treated patients had a significantly greater increase in global akathisia scores (P = .01) and significant weight increase (mean [SD] = 3.5 [11.8] kg, or 7.7 [26.1] lb) compared to placebo (1.0 [6.4] kg, or 2.2 [14.1] lb) (P = .03). No significant changes in AIMS scores were observed for either treatment group. Conclusions Adjunctive ziprasidone, added to escitalopram, led to a greater weight gain and greater but modest akathisia compared to placebo. The effect of ziprasidone on QTc showed a trend toward significance, and therefore caution should be used in the administration of ziprasidone. While ziprasidone augmentation in patients with MDD appears safe, precautions should be taken in practice, specifically regular monitoring of electrocardiogram, weight, extrapyramidal symptoms, and involuntary movements. Trial registration ClinicalTrials.gov identifier: NCT00633399​​.

Purpose The purpose of this study was to assess the association of obsessive-compulsive symptoms (OCS) with suicide risk among college students. Methods Subjects were 474 college students who attended mental health screenings at two private universities and completed multiple self-report questionnaires. Results Presence of one or more OCS was associated with an increased odds ratio of suicide risk of approximately 2.4, although this was no longer a significant risk factor when controlling for depressive symptoms. Of the OCS assessed, only obsessions about speaking or acting violently remained an independent risk factor for suicidality over and above depression. Conclusions Although our study was cross-sectional in nature and thus cannot determine causality, increased burden of particular OCS symptom clusters, such as violent or aggressive obsessions, may increase risk among college students, for suicidal ideation.

The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures.Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group.Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.