1H MRS Measurement of Cortical GABA and Glutamate in Primary Insomnia and Major Depressive Disorder: Relationship to Sleep Quality and Depression Severity.

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.

Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial.

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.

Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial.

Objective: Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). Background: t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress. Materials and methods: We conducted a double-blind, sham-controlled study on the safety and efficacy [change in Hamilton Depression Rating Scale (HAM-D17) total score at end-point] of adjunct t-PBM NIR [823 nm; continuous wave (CW); 28.7 × 2 cm2; 36.2 mW/cm2; up to 65.2 J/cm2; 20-30 min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed. Results: The effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen's d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events. Conclusions: t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.

Mechanisms of Perceived Treatment Assignment and Subsequent Expectancy Effects in a Double Blind Placebo Controlled RCT of Major Depression.

Objective: It has been suggested that patients' perception of treatment assignment might serve to bias results of double blind randomized controlled trials (RCT). Most previous evidence on the effects of patients' perceptions and the mechanisms influencing these perceptions relies on cross-sectional associations. This re-analysis of a double blind, placebo controlled RCT of pharmacological treatment of major depression set out to gather longitudinal evidence on the mechanism and effects of patients' perceived treatment assignment in the pharmacological treatment of major depression. Methods: One-hundred eighty-nine outpatients with DSM-IV diagnosed major depression were randomized to SAMe 1,600-3,200 mg/d, escitalopram 10-20 mg/days, or placebo for 12 weeks. Data on depressive symptoms (17-item Hamilton Depression Scale; HDRS-17), adverse events and patients' perceived treatment assignment was collected at baseline, week 6, and week 12. The re-analysis focused on N = 166 (out of the originally included 189 participants) with available data on perceived treatment assignment. Results: As in the parent trial, depressive symptoms (HDRS-17) significantly decreased over the course of 12 weeks and there was no difference between placebo, SAMe or escitalopram. A significant number of patients changed their perceptions about treatment assignment throughout the trial, especially between baseline and week 6. Improvement in depressive symptoms, but not adverse events significantly predicted perceived treatment assignment at week 6. In turn, perceived treatment assignment at week 6, but not actual treatment, predicted further improvement in depressive symptoms at week 12. Conclusions: The current results provide longitudinal evidence that patients' perception of treatment assignment systematically change despite a double blind procedure and in turn might trigger expectancy effects with the potential to bias the validity of an RCT. Parent study grant number: R01 AT001638 Parent study ClinicalTrials. gov Identifier: NCT00101452.

Gamma Ventral Capsulotomy in Intractable Obsessive-Compulsive Disorder.

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.

Neurocognitive function in paediatric obsessive-compulsive disorder.

OBJECTIVES: The small body of neuropsychological research in paediatric obsessive-compulsive disorder (OCD) yields inconsistent results. A recent meta-analysis found small effect sizes, concluding that paediatric OCD may not be associated with cognitive impairments, stressing the need for more research. We investigated neuropsychological performance in a large sample of youths with OCD, while assessing potential moderators. METHODS: Participants with OCD (n = 102) and matched controls (n = 161) were thoroughly screened and blindly evaluated for comorbidities, and completed a neuropsychological battery assessing processing speed, visuospatial abilities (VSA), working memory (WM), non-verbal memory (NVM), and executive functions (EF). RESULTS: Compared to controls, youths with OCD exhibited underperformance on tasks assessing processing speed. On tests of VSA and WM, underperformance was found only on timed tasks. There were no differences on NVM and EF tasks. Notably, the OCD group's standardised scores were in the normative range. Test performance was not associated with demographic or clinical variables. CONCLUSIONS: Youths with OCD exhibited intact performance on memory and EF tests, but slower processing speed, and underperformance only on timed VSA and WM tasks. While the OCD group performed in the normative range, these findings reveal relative weaknesses that may be overlooked. Such an oversight may be of particular importance in clinical and school settings.

Standardization of health outcomes assessment for depression and anxiety: recommendations from the ICHOM Depression and Anxiety Working Group.

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.

A Pilot, Randomized Controlled Study of Tai Chi With Passive and Active Controls in the Treatment of Depressed Chinese Americans.

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.

Empathic nonverbal behavior increases ratings of both warmth and competence in a medical context.

In medicine, it is critical that clinicians demonstrate both empathy (perceived as warmth) and competence. Perceptions of these qualities are often intuitive and are based on nonverbal behavior. Emphasizing both warmth and competence may prove problematic, however, because there is evidence that they are inversely related in other settings. We hypothesize that perceptions of physician competence will instead be positively correlated with perceptions of physician warmth and empathy, potentially due to changing conceptions of the physician's role. We test this hypothesis in an analog medical context using a large online sample, manipulating physician nonverbal behaviors suggested to communicate empathy (e.g. eye contact) and competence (the physician's white coat). Participants rated physicians displaying empathic nonverbal behavior as more empathic, warm, and more competent than physicians displaying unempathic nonverbal behavior, adjusting for mood. We found no warmth/competence tradeoff and, additionally, no significant effects of the white coat. Further, compared with male participants, female participants perceived physicians displaying unempathic nonverbal behavior as less empathic. Given the significant consequences of clinician empathy, it is important for clinicians to learn how nonverbal behavior contributes to perceptions of warmth, and use it as another tool to improve their patients' emotional and physical health.

Differentiating residual symptoms of depression from adverse events among patients initiating treatment with an antidepressant.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Guarding the Gate: Remote Structured Assessments to Enhance Enrollment Precision in Depression Trials.

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.

Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants.

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 [≥300mg/day], aripiprazole [≤2.5mg/day], or sertraline [≥150mg/day]) were randomized to naltrexone 1mg 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.

Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Cardiac, Endocrine, Metabolic, and Motoric Effects in a Randomized, Double-Blind, Placebo-Controlled Study.

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​​.

The Effectiveness of Telepsychiatry-Based Culturally Sensitive Collaborative Treatment for Depressed Chinese American Immigrants: A Randomized Controlled Trial.

OBJECTIVE: This study evaluates the effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention to improve treatment outcomes for depressed Chinese American immigrants. METHODS: Participants were Chinese Americans recruited from primary care settings from February 1, 2009, to July 31, 2012, with DSM-IV major depressive disorder (MDD) identified by the Mini-International Neuropsychiatric Interview. Eligible patients were randomized to receive either T-CSCT or treatment as usual (TAU) for 6 months. T-CSCT involves (1) cultural consultation via videoconference and (2) care management. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17); positive response was defined as a ≥ 50% decrease in HDRS17 score, and remission was defined as HDRS17 score ≤ 7. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Outcomes were compared using multivariate logistic regression and mixed-model for repeated measures methods. RESULTS: Among participants (N = 190), 63% were female, and the mean (SD) age was 50 (14.5) years. They were randomized to T-CSCT (n = 97; 51%) or TAU (n = 93; 49%). Using multivariate logistic regression analyses, the odds of achieving response and remission were significantly greater for the T-CSCT group compared to the control group (odds ratio [OR] = 3.9 [95% CI, 1.9 to 7.8] and 4.4 [95% CI, 1.9 to 9.9], respectively). Multivariate general linear model analyses showed that patients in the T-CSCT group had significantly greater improvement over time in HDRS17 (F4,95 = 4.59, P = .002), CGI-S (F4,95 = 4.22, P = .003), and CGI-I (F4,95 = 2.95, P = .02) scores. CONCLUSIONS: T-CSCT is effective in improving treatment outcomes of Chinese immigrants with MDD. TRIAL REGISTRATION: ClincialTrials.gov identifier: NCT00854542.

Ziprasidone augmentation for anxious depression.

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.

Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study.

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 < .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS6) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P < .01) and HDRS28-SI (P < .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29%) maintained their remission throughout a 3-month naturalistic follow-up. 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.

A placebo-controlled crossover study of iloperidone augmentation for residual anger and irritability in major depressive disorder.

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.

Obsessive-Compulsive Symptoms as a Risk Factor for Suicidality in U.S. College Students.

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.

Rapid Learning of Adverse Medical Event Disclosure and Apology.

INTRODUCTION: Despite published recommended best practices for full disclosure and apology to patients and families after adverse medical events, actual practice can be inadequate. The use of "cognitive aids" to help practitioners manage complex critical events has been successful in a variety of fields and healthcare. We wished to extend this concept to disclosure and apology events. The aim of this study was to test if a brief opportunity to review a best practice guideline for disclosure and apology would improve communication performance. METHODS: Thirty pairs of experienced obstetricians and labor nurses participated in a 3-part exercise with mixed-realism simulation. The first part used a standardized actor patient to meet the obstetrical team. The second part used a high-fidelity simulation leading to an adverse medical event (retained sponge), and the third part used standardized actors, patient, and husband, who systematically move through stages of grief response. The participants were randomized into 2 groups, one was provided with a cognitive aid in the form of a best practice guideline for disclosure and apology and the other was only given time to plan. Four blinded raters working in pairs scored subjects on a 7-point scale using a previously developed assessment instrument modified for this study. RESULTS: Pooled ratings of the disclosure and apology discussion for the intervention group (n = 167, mean = 4.9, SD = 0.92) were higher than those from the control group (n = 167, mean = 4.3, SD = 1.21) (P < 0.0001). One specific element was rated higher for the intervention group than the control group; posture toward the patient (n = 27, mean = 5.1, SD = 0.82 versus n = 28, mean = 4.3, SD = 1.33) (P = 0.020). The elements of dealing with anger, dealing with depression, dealing with denial, bargaining, and acceptance were not different. CONCLUSIONS: Experienced practitioners performed better in a simulated disclosure and apology conversation after reviewing a cognitive aid in the form of a best practice guideline than a control group that was only given time to prepare.

Prevalence and impact of obsessive-compulsive symptoms in depression: a STAR*D report.

OBJECTIVE: Obsessive-compulsive symptoms (OCS) may be underrecognized in patients suffering from major depressive disorder. These patients may not receive optimal psychopharmacologic or psychological treatment if their OCS are not attended to. We performed a secondary analysis of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial database, the largest effectiveness study of "real-world" depression ever conducted, to determine the frequency of OCS and their effects on depression outcome. METHOD: 3,984 adult subjects without a previous selective serotonin reuptake inhibitor trial for their current major depressive episode, per DSM-IV diagnostic criteria, had data for rating scales of interest at entry into Level 1 of the STAR*D trial, a 12-week open trial of citalopram at a dose of 20-60 mg/d to assess rates of depression remission. Our primary interest was the OCD subscale of the Psychiatric Diagnostic Screening Questionnaire. RESULTS: At study entry, 53% of the STAR*D sample (which excluded patients with primary obsessive-compulsive disorder) endorsed ≥ 1 OCS, and 14% endorsed ≥ 4 OCS. Subjects endorsing ≥ 4 OCS had significantly lower corrected odds of depression remission on both the 17-item Hamilton Depression Rating Scale (HDRS-17) (OR = 0.61) and the Quick Inventory of Depressive Symptomatology (odds ratio [OR] = 0.51). Number of OCS endorsed was positively correlated with HDRS-17 score (r = 0.26, P < .0001). Consistent with findings from the Dunedin, New Zealand Community Study, the most common obsessions were doubts of having inadvertently caused harm and violent obsessions. CONCLUSIONS: OCS are common in depressed outpatients and are often not attended to. They impact clinical recovery from depression and should be screened for since sufferers are often reluctant to disclose these symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00021528.