Effect of next-step antidepressant treatment on suicidal ideation: findings from the VAST-D trial.

BACKGROUND: Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a 'next-step'. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted. METHOD: The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored. RESULTS: Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to 'next-step' treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI. CONCLUSION: SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

Continuation phase treatment outcomes for switching, combining, or augmenting strategies for treatment-resistant major depressive disorder: A VAST-D report.

BACKGROUND: This secondary analysis of the VA Augmentation and Switching Treatments for Depression study compared the continuation phase treatment outcomes of three commonly used second-step treatment strategies following at least one prior failed medication treatment attempt. METHODS: In total, 1522 outpatients with MDD were randomized to switching to bupropion-SR (S-BUP), combining with bupropion-SR (C-BUP), or augmenting with aripiprazole (A-ARI). Following 12 weeks of acute phase treatment, 725 entered the 24-week continuation treatment phase. Depressive symptom severity, relapse, "emergent" remission, anxiety, suicidal ideation, quality of life, health status, and side effects were compared. RESULTS: We did not find clinically significant differential treatment effects with the exception that A-ARI was associated with less anxiety than S-BUP or C-BUP. Participants who entered continuation treatment as remitters had milder depressive symptom severity and lower relapse rates than those not in remission; they also experienced more improvement on most other outcomes. A-ARI was associated with less anxiety, insomnia, and dry mouth but more somnolence, extrapyramidal effects, akathisia, abnormal laboratory values, and appetite and weight gain. CONCLUSIONS: Continuation treatment is a dynamic period. Regardless of the treatment, participants who entered continuation treatment at Week 12 in full remission continued to have better outcomes over the subsequent 24 weeks than those who were not in remission at the start of the continuation phase.

Cognitive Processing Therapy for Posttraumatic Stress Disorder Is Associated with Negligible Change in Subjective and Objective Sleep.

Background: Patients receiving Cognitive Processing Therapy (CPT), an evidence based therapy for posttraumatic stress disorder (PTSD), report improved sleep quality. However, the majority of studies have examined residual sleep disturbance via self-report surveys or separate items on PTSD measures. This study examined whether CPT delivered to veterans in a VA setting improved sleep indices using state-of-the-art objective and subjective insomnia measures. Participants: Participants were war veterans with a current PTSD diagnosis scheduled to begin outpatient individual or group CPT at two Veteran's Affairs (VA) locations (n = 37). Methods: Sleep symptom severity was assessed using the recommended research consensus insomnia assessment, the consensus daily sleep diary and actigraphy. PTSD symptomatology pre- and post-treatment were assessed using the Clinician Administered PTSD Scale. Results: A small to moderate benefit was observed for the change in PTSD symptoms across treatment (ESRMC = .43). Effect sizes for changes on daily sleep diary and actigraphy variables after CPT were found to be negligible (Range ESRMC = - .16 to .17). Sleep indices remained at symptomatic clinical levels post-treatment. Discussion: These findings support previous research demonstrating a need for independent clinical attention to address insomnia either before, during, or after PTSD treatment.

The Effect of Sleep Disorders, Sedating Medications, and Depression on Cognitive Processing Therapy Outcomes: A Fuzzy Set Qualitative Comparative Analysis.

Cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) is an effortful process requiring engagement in cognitive restructuring. Sleep disorders may lead to avoidance of effortful tasks and cognitive performance deficits. We explored whether sleep disorders, as assessed by polysomnography, were consistently associated with treatment response in combination with other factors. This study included 32 U.S. veterans who were examined both before and after CPT for combat-related PTSD. We employed a novel, case-comparative technique, fuzzy set qualitative comparative analysis (fsQCA), to identify combinations of fuzzy and crisp factors (recipes) that achieve a clinically significant outcome. Approximately one-quarter of cases experiencing clinically significant change were either (a) Vietnam era veterans without sedating medications, moderate sleep disordered breathing, and severe depression; or (b) non-Vietnam era veterans with sedating medications and without severe periodic limb movements (or significant periodic limb movement arousals). Recipes involving the absence of the relevant sleep disorder were associated with the highest coverage values. These results using fsQCA (a) provide valuable information about the heterogeneity of CPT response and (b) suggest that sleep disorders are important factors to consider in theoretical discussions of who responds to CPT for PTSD.

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.

Prognostic implications of paranoia and thought disorder in new onset psychosis.

This study follows a group of 174 young people with new onset of schizotypal symptoms and examines factors which may lead to conversion to psychosis. These prodromal subjects were screened for symptoms and later given the Structured Clinical Interview of DSM-III-R at one year, two years and ten years post onset. We also included the Paranoia Scale of Fenigstein and Vanable and the Scale for Thought, Language and Communications of Andreasen in all interviews. Our analysis found that the addition of scales for paranoia and thought disorder enhanced prediction of conversion to psychosis and long term outcome. The early occurrence of ideas of reference and poverty of thought appear to be significant predictors of future deterioration even when considered among other high-risk variables.

Psilocybin and Obsessive Compulsive Disorder.

Obsessive Compulsive Disorder (OCD) is a psychiatric disorder with considerable morbidity and mortality. This condition disables many individuals and is often refractory to treatment. Research suggests that serotonin plays a role in OCD symptom reduction. We present a case of an individual who successfully used psilocybin, a serotonergic agent, to reduce the core symptoms of OCD for several years. Although not endorsing this form of treatment, we feel that the successful use of this agent highlights the role of serotonergic factors in OCD and the need for further, legitimate research into the value of psilocybin in the treatment of anxiety disorders.

Hyperbaric nursing.

The varied clinical applications for hyperbaric oxygen therapy have led to the development of a unique, highly skilled nursing specialty of hyperbaric nursing. The ever-increasing availability of hyperbaric medicine and the broadening scope of clinical indications have fueled the need for highly skilled hyperbaric nurses.

Accuracy of physician gestalt in prediction of significant abdominal and pelvic injury in adult blunt trauma patients.

OBJECTIVE: Focusing on potential missed injury rates and sensitivity of low-risk of injury predictions, we sought to evaluate the accuracy of physician gestalt in predicting clinically significant injury (CSI) in the abdomen and pelvis among blunt trauma patients presenting to the emergency department (ED). METHODS: We collected gestalt data on physicians caring for adult blunt trauma patients who received abdominal/pelvic computed tomography (CT) at three Level I and one Level II trauma centers. The primary outcome of CSI was defined as injury on abdominal/pelvic CT requiring hospitalization or intervention. Physicians evaluating trauma patients estimated the likelihood of CSI prior to abdominal/pelvic CT review (response choices: <2%, 2%-10%, 11%-20%, 21%-40%, >40%). We evaluated potential missed injury rates (prevalence of CSI) and sensitivity for prediction categories, as well as calibration and area under the receiver operating characteristic (AUROC) curve for overall physician gestalt. RESULTS: Of 2030 patients, 402 (20%) had an injury on abdominal/pelvic CT and 270 (13%) had CSI. The <2% risk of CSI gestalt cutoff had a potential missed injury rate of 5.6% and a sensitivity of 95.2% (95% confidence interval [CI] 91.7%-97.3%). The 0%-10% cutoff of CSI gestalt had a potential missed injury rate of 6.3% (95% CI, 5.0%-7.9%) and a sensitivity of 75.2% (95% CI 69.5%-80.1%). With an overall AUROC of 0.699 (95% CI 0.679-0.719), physician gestalt was moderately accurate and calibrated for the midranges of predicted risk but poorly calibrated at the extremes. CONCLUSIONS: Physician gestalt for the prediction of adult abdominal and pelvic CSI is moderately accurate and calibrated. However, the potential missed CSI rate and low sensitivity of the low perceived risk of injury cutoffs indicate that gestalt by itself is insufficient to direct selective abdominal/pelvic CT use in adult blunt trauma patient evaluation.

Predictive value of thought disorder in new-onset psychosis.

OBJECTIVE: This research addresses the relationship of formal thought disorder in the early stages of psychotic illness to the long-term outcome of mental health many years later. The specific topic of concern was to evaluate the prognostic significance of thought disorder on the severity of psychosis over time. METHODS: Subjects with new-onset psychosis were evaluated on a variety of measures including education, physical health, Brief Psychiatric Rating Scale scores. They were also given the Thought, Language, and Communication Scale to evaluate thought disorder. Subjects were interviewed again at 10 and 20 years to evaluate variations in outcome. Appropriate statistical methods were used to evaluate changes in the level of functioning over time. RESULTS: Thought disorder was not unique to schizophrenia. Bipolar patients presented with significant positive thought disorder at the onset of psychosis. Overtime positive thought disorder gradually improved in most patients. Negative thought disorder was more persistent, especially in subjects with schizophrenia. Initial psychosis with thought disorder characterized by poverty of content seemed to be associated with poor long-term outcome. CONCLUSION: Formal thought disorder can predict outcome in some cases of psychosis. Not all types of thought disorder have the same prognostic implication. Positive forms of thought disorder (pressured speech, tangentiality) had no significant predictive value. Negative thought disorder (particularly poverty of speech and poverty of content) tend to predict a chronic, more unrelenting course of illness.

Psychoactive properties of alpha-methyltryptamine: analysis from self reports of users.

This is a retrospective examination of former users of alpha-methyltryptamine (AMT). A scale of questions was given to subjects who were familiar with the effects of AMT and the outcome was analyzed. Most subjects agreed that AMT had strong hallucinogenic qualities. The most common unwanted effects included anxiety, nausea and moderately severe dysphoria. Several subjects reported significant depression associated with use of AMT. Use of alpha-methyltryptamine could be dangerous in individuals prone to depression.

More frequent visits to wound care clinics result in faster times to close diabetic foot and venous leg ulcers.

OBJECTIVE: To determine whether patients with Wagner grades 1 and 2 diabetic foot ulcers (DFUs) or venous leg ulcers (VLUs) differed in terms of time to close depending on visit frequency to wound care centers. DESIGN: Retrospective cohort study. SETTING: Outpatients wound care centers. PATIENTS: Two hundred six patients with Wagner grade 1 or 2 DFUs and 215 patients with VLUs in the lower extremities collected from 9 wound care centers in 5 states (6 states for VLUs) during 2009/2010 and whose wounds had closed. INTERVENTIONS: For each type of DFU/VLU, 1 group had every-other-week visits, defined as more than 10 days between visits in the first 4 weeks, whereas the other group had weekly visits, defined as at least once a week. MAIN OUTCOMES MEASURES: Median time to close. MAIN RESULTS: For patients with DFUs, 63.8% of wounds had closed in the weekly visit group after 4 weeks compared with 2.0% in the every-other-week group (P = 2.3 × 10); for patients with VLUs, 78 of 105 wounds (52%) closed in the weekly visit group compared with 0% in the every-other-week group (P = 2.40 × 10). After controlling for all covariates in a Cox regression model, median time to close for weekly patients was 28 days versus 66 days for patients seen every other week. Adjusted median times to close VLUs in the same groups were 25 versus 55 days. CONCLUSIONS: More frequent visits can be extremely beneficial, with implications of lower costs and higher quality of life for patients.

Doxycycline as a modulator of inflammation in chronic wounds.

 Doxycycline is a semisynthetic, chemically modified tetracycline compound that is rapidly absorbed and exerts biological effects independent of its antimicrobial activity. One such effect includes the inhibition of matrix metalloproteinases. Doxycycline has a long history as a collagenase inhibitor. This article will describe its mode of action and review its effectiveness in significantly reducing inflammation and elevated levels of proinflammatory cytokines within chronic wounds. .

Piloting a Graduate Medical Education Point-of-Care Ultrasound Curriculum.

Objective As point-of-care ultrasound (POCUS) use grows, training in graduate medical education (GME) is increasingly needed. We piloted a multispecialty GME POCUS curriculum and assessed feasibility, knowledge, and comfort with performing POCUS exams. Methods Residents were selected from the following residency programs: internal medicine, family medicine, emergency medicine, and a combined internal medicine/pediatrics program. Didactics occurred through an online curriculum that consisted of five modules: physics and machine operation, cardiac, lung, soft tissue, and extended focused sonography in trauma applications. Residents completed a pre- and post-curriculum questionnaire, as well as knowledge assessments before and after each module. One-hour hands-on training sessions were held for each module. Differences between pre- and post-participation questionnaire responses were analyzed using the Wilcoxon rank sum. Results Of the 24 residents selected, 21 (86%) were post-graduate year two or three, and 16 (65%) were from the internal medicine program. Eighteen (67%) residents reported limited prior POCUS experience. All pre- to post-knowledge assessment scores increased (p<0.05). Statistically significant increases pre- to post-curriculum were found for frequency of POCUS use (p = 0.003), comfort in using POCUS for assessing for abdominal aortic aneurysm, soft tissue abscess detection, undifferentiated hypotension and dyspnea, cardiac arrest and heart failure (p<0.025); and competency in machine use, acquiring and interpreting images and incorporating POCUS into clinical practice (p<0.001). All participants felt the skills learned during this curriculum were essential to their future practice. Conclusions In this pilot, we found using a combination of online and hands-on training to be feasible, with improvement in residents' knowledge, comfort, and use of POCUS.

Impact of Concurrent Posttraumatic Stress Disorder on Outcomes of Antipsychotic Augmentation for Major Depressive Disorder With a Prior Failed Treatment: VAST-D Randomized Clinical Trial.

OBJECTIVE: To determine whether concurrent posttraumatic stress disorder (PTSD) should affect whether to augment or switch medications when major depressive disorder (MDD) has not responded to a prior antidepressant trial. METHODS: Patients at 35 Veterans Health Administration medical centers from December 2012 to May 2015 with nonpsychotic MDD (N = 1,522) and a suboptimal response to adequate antidepressant treatment were randomly assigned to 3 "next step" treatments: switching to bupropion, augmenting the current antidepressant with bupropion, and augmenting with the antipsychotic aripiprazole. Blinded ratings with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) determined remission and response by 12 weeks and relapse after remission. Survival analyses compared treatment effects in patients with concurrent PTSD diagnosed with the Mini-International Neuropsychiatric Interview (n = 717, 47.1%) and those without PTSD (n = 805, 52.9%). RESULTS: Patients diagnosed with PTSD showed more severe depressive symptoms at baseline and were less likely to achieve either remission or response by 12 weeks. Augmentation with aripiprazole was associated with greater likelihood of achieving response (68.4%) than switching to bupropion (57.7%) in patients with PTSD (relative risk [RR] = 1.26; 95% CI, 1.01-1.59) as well as in patients without PTSD (RR = 1.29; 95% CI, 1.05-1.97) (78.9% response with aripiprazole augmentation vs 66.9% with switching to bupropion). Treatment comparisons with the group receiving augmentation with bupropion were not significant. There was no significant interaction between treatment group and PTSD on remission (P = .70), response (P = .98), or relapse (P = .15). CONCLUSIONS: Although PTSD was associated with poorer overall outcomes, the presence of concurrent PTSD among Veterans in this trial did not affect the comparative effectiveness of medications on response, remission, or relapse after initial remission. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01421342.

Movement disorders and MDMA abuse.

This article present the cases of two young men with chronic MDMA abuse who later developed movement disorders typical of the Parkinson's syndrome. It is worth noting that both men bought the presumed MDMA from the same illicit source. Potential risks of MDMA use and movement disorders are discussed. The risks inherent from contaminants and similar factors associated with illegal drug manufacture are discussed. The authors conclude that as long as nonpharmaceutical-grade MDMA is illicitly produced, health risks will be associated with its use.

Reconsidering formative measurement.

The relationship between observable responses and the latent constructs they are purported to measure has received considerable attention recently, with particular focus on what has become known as formative measurement. This alternative to reflective measurement in the area of theory-testing research is examined in the context of the potential for interpretational confounding and a construct's ability to function as a point variable within a larger model. Although these issues have been addressed in the traditional reflective measurement context, the authors suggest that they are particularly relevant in evaluating formative measurement models. On the basis of this analysis, the authors conclude that formative measurement is not an equally attractive alternative to reflective measurement and that whenever possible, in developing new measures or choosing among alternative existing measures, researchers should opt for reflective measurement. In addition, the authors provide guidelines for researchers dealing with existing formative measures.

Risk factors and prevention in adolescent substance abuse: a biopsychosocial approach.

This article provides an overview of existing evidence regarding risk and prevention factors in adolescent substance abuse from a biopsychosocial viewpoint. It is believed that this approach offers a practical model for the integration of inherently complex factors into the clinical setting. These factors cannot be isolated from the influences of the greater society, such as the school system or homelessness. Prevention and treatment issues must approach the impaired adolescent with a multifactorial and comprehensive plan that integrates multidisciplinary involvement.

Characteristics of U.S. Veteran Patients with Major Depressive Disorder who require "next-step" treatments: A VAST-D report.

OBJECTIVE: Finding effective and lasting treatments for patients with Major Depressive Disorder (MDD) that fail to respond optimally to initial standard treatment is a critical public health imperative. Understanding the nature and characteristics of patients prior to initiating "next-step" treatment is an important component of identifying which specific treatments are best suited for individual patients. We describe clinical features and demographic characteristics of a sample of Veterans who enrolled in a "next-step" clinical trial after failing to achieve an optimal outcome from at least one well-delivered antidepressant trial. METHODS: 1522 Veteran outpatients with nonpsychotic MDD completed assessments prior to being randomized to study treatment. Data is summarized and presented in terms of demographic, social, historical and clinical features and compared to a similar, non-Veteran sample. RESULTS: Participants were largely male and white, with about half unmarried and half unemployed. They were moderately severely depressed, with about one-third reporting recent suicidal ideation. More than half had chronic and/or recurrent depression. General medical and psychiatric comorbidities were highly prevalent, particularly PTSD. Many had histories of childhood adversity and bereavement. Participants were impaired in multiple domains of their lives and had negative self-worth. LIMITATIONS: These results may not be generalizable to females, and some characteristics may be specific to Veterans of US military service. There was insufficient data on age of clinical onset and depression subtypes, and three novel measures were not psychometrically validated. CONCLUSIONS: Characterizing VAST-D participants provides important information to help clinicians understand features that may optimize "next-step" MDD treatments.