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.

Factors Affecting Antidepressant Response Trajectories: A Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes Trial Report.

Background: In this secondary analysis of the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study we used antidepressant response trajectories to assess the association of treatment and multiple clinical/demographic factors with the probability of response. Methods: Using data from VAST-D, a multi-site, randomized, single-blind trial with parallel-assignment to one of three treatment interventions in 1522 Veterans whose major depressive disorder was unresponsive to at least one antidepressant trial, we evaluated response patterns using group-based trajectory modeling (GBTM). A weighted multinomial logistic regression analysis with backward elimination and additional exploratory analyses were performed to evaluate the association of multiple clinical/demographic factors with the probability of inclusion into specific trajectories. Additional exploratory analyses were used to identify factors associated with trajectory group membership that could have been missed in the primary analysis. Results: GBTM showed the best fit for depression symptom change was comprised of six trajectories, with some trajectories demonstrating minimal improvement and others showing a high probability of remission. High baseline depression and anxiety severity scores decreased, and early improvement increased, the likelihood of inclusion into the most responsive trajectory in both the GBTM and exploratory analyses. Conclusion: While multiple factors influence responsiveness, the probability of inclusion into a specific depression symptom trajectory is most strongly influenced by three factors: baseline depression, baseline anxiety, and the presence of early improvement.

Comparison of Suicidal Ideation and Depressive Symptoms Between Medical and Pharmacy Students.

Objective. The purpose of the study was to compare suicidal ideation among medical and pharmacy students and characterize related symptoms.Methods. The authors conducted a cross-sectional, retrospective study to compare suicidal ideation among medical and pharmacy students at a single public university during 2009 to 2020. Respondents' voluntary and anonymous responses to the Interactive Screening Program (ISP) Stress and Depression Questionnaire are reported.Results. The authors analyzed responses from 619 medical and 214 pharmacy students collected over 11 academic years. There was no significant difference between medical and pharmacy students who endorsed suicidal ideation (13.5% vs 17.3%, respectively). The Patient Health Questionnaire-9 (PHQ-9) scores were significantly different between medical and pharmacy students, with more pharmacy students reporting moderate to severe depression (24.3% for medical vs 35.1% for pharmacy). Compared to medical students, more pharmacy students also endorsed anhedonia, a reduced capacity for pleasure (13.4% vs 24.3%, respectively), sleep problems (29.6% vs 42.6%, respectively), and fatigue (46% vs 64.4%, respectively). Pharmacy students also reported more intense affective states such as "feeling your life is too stressful" and "feeling intensely anxious or having anxiety attacks." Relationships and physical/mental health/substance abuse were common themes that emerged from the qualitative data.Conclusion. While there was no significant difference in suicidal ideation between pharmacy and medical students, the prevalence is alarming compared to the general population. More pharmacy students endorsed symptoms of depression and intense affective states that could impair functioning. Future studies may focus on mitigation strategies for suicidal ideation among health professions students.

Long-term outcomes in MEN-1 patients with pancreatic neuroendocrine neoplasms: an Israeli specialist center experience.

PURPOSE: The decreased life expectancy of MEN-1 patients is mainly related to pancreatic neuroendocrine tumors (pNETs). At best, limited data is available on the natural history of MEN-1-associated pNETs, as these tumors are rare and have a wide range of biologic behavior. Our study aims to explore the clinical course of patients with MEN-1-associated pNETs and the long-term outcomes. METHODS: This longitudinal study was conducted on the MEN-1 cohort treated at our referral center over a 22-year period (1996-2018). Relevant clinical data were retrospectively analysed. RESULTS: Among the 33 MEN-1 patients included in our study, pNETs were identified in 21 subjects with a penetrance of 48% by the age of 50. Non-functioning and functioning pNETs were diagnosed in sixteen (76%) and five (24%) patients, respectively. Two-thirds of the patients had multifocal tumors. The median number of pancreatic macroscopic lesions per individual was 4.0 ± 3.9 (range 1-8) with a mean size of 1.3 ± 2.1 cm (range 0.5-10). The metastatic rate according to the dominant pNET lesion reached 100%, 62% and 6% for tumors sized > 4 cm, 2.1-4 cm, and 1-2 cm, respectively. Over the study period, one or more therapeutic interventions for pNETs were required in 20 out of the 21 patients. pNET-related metastatic complication was the main cause of death within this MEN-1 cohort. The overall survival rate for the pNETs patients was 86% during a mean follow-up period of 8.0 ± 4.6 years. CONCLUSIONS: In our MEN-1 cohort, non-functioning pNETs were the most frequent type of pancreaticoduodenal tumor, and the tumor size correlated with the risks of metastasis and death. Increased awareness, early diagnosis, and a multidisciplinary approach may improve the associated morbidity and mortality in these patients.

Gender differences among medical students, house staff, and faculty physicians at high risk for suicide: A HEAR report.

BACKGROUND: In comparison with the general population, physicians, and physicians-in-training are at greater risk for suicide. Although key gender differences in suicide risk factors and behaviors have been identified in the general population, the extent to which these differences apply to physicians and physicians-in-training is unclear. Here, we aimed to identify gender differences in risk factors, clinical presentation, and help-seeking behaviors of medical students, house staff, and physician faculty at high risk for suicide. METHODS: We explored gender differences among 450 physicians and trainees meeting criteria for high suicide risk on anonymous online questionnaires completed between 2009 and 2017. RESULTS: High-risk female trainees and physicians had higher mean Patient Health Questionnaire-9 (PHQ-9) scores compared with the males (11.1, standard deviation [SD] 5.1 vs. 9.8, SD 4.7) and were more likely to endorse feeling worried (73.8% vs. 61.2%), irritable (60.4% vs. 49.4%), and stressed (79.6% vs. 70%). High-risk male trainees and physicians were more likely than females to endorse suicidal thoughts (31.2% vs. 22.1%), intense anger (24.3% vs. 16.1%), drinking too much (31.2% vs. 22.3%), and recreational drug or prescription medication use without clinically appropriate follow-up (9.4% vs. 4.3%). There were no gender differences in help-seeking behaviors. CONCLUSIONS: This is the first study to report gender differences among risk factors, presentation, and help-seeking behaviors of physicians, and trainees at high risk for suicide. Our findings are mostly consistent with those of the general population and show that only a minority of at-risk men and women in healthcare sought treatment, highlighting the importance of intervention and suicide prevention in this population.

Endoscopic Ultrasound-Guided Radiofrequency Ablation: A New Therapeutic Approach for Pancreatic Neuroendocrine Tumors.

CONTEXT: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is rapidly emerging as feasible therapy for patients with pancreatic neuroendocrine tumors (pNETs) in selected cases, as a result of its favorable safety profile. OBJECTIVE: To assess the feasibility, safety, and efficacy of EUS-RFA in a cohort of patients with functional and nonfunctional pNETs (NF-pNETs). DESIGN: Data on pNET patients treated with EUS-RFA between March 2017 and October 2018 at two tertiary centers was retrospectively analyzed. RESULTS: The cohort included 18 adults (eight women, 10 men), aged 60.4 ± 14.4 years (mean ± SD), seven insulinoma patients, and 11 patients with NF-pNETs. Twenty-seven lesions with a mean diameter of 14.3 ± 7.3 mm (range 4.5 to 30) were treated. Technical success defined as typical postablative changes on a surveillance imaging was achieved in 26 out of 27 lesions. Clinical response with normalization of glucose levels was observed in all (seven of seven) insulinoma cases within 24 hours of treatment. Overall, there were no major complications 48 hours postprocedure. No clinically significant recurrences were observed during mean follow-up of 8.7 ± 4.6 months (range 2 to 21 months). CONCLUSIONS: EUS-guided RFA of pNETs is a minimally invasive, safe, and technically feasible procedure for selected patients.

General Predictors and Moderators of Depression Remission: A VAST-D Report.

OBJECTIVE: Almost two-thirds of patients with major depressive disorder do not achieve remission with initial treatments. Thus, identifying and providing effective, feasible, and safe "next-step" treatments are clinical imperatives. This study explores patient baseline features that might help clinicians select between commonly used next-step treatments. METHODS: The authors used data from the U.S. Department of Veterans Affairs (VA) Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, a multisite, randomized, single-blind trial of 1,522 Veterans Health Administration patients who did not have an adequate response to at least one course of antidepressant treatment meeting minimal standards for dosage and duration. For 12 weeks, participants received one of three possible next-step treatments: switch to another antidepressant-sustained-release bupropion; combination with another antidepressant-sustained-release bupropion; or augmentation with an antipsychotic-aripiprazole. Life table regression models were used to identify baseline characteristics associated with remission overall (general predictors) and their interaction with remission among the three treatment groups (moderators). RESULTS: Remission was more likely for individuals who were employed, less severely and chronically depressed, less anxious, not experiencing complicated grief symptoms, did not experience childhood adversity, and had better quality of life and positive mental health. Two features suggested specific next-step treatment selections: age ≥65 years (for whom augmentation with aripiprazole was more effective than switch to bupropion) and severe mixed hypomanic symptoms (for which augmentation with aripiprazole and combination with bupropion were more effective than switch to bupropion). CONCLUSIONS: If replicated, these preliminary findings could help clinicians determine which patients with depression requiring next-step treatment will benefit most from a specific augmentation, combination, or switching strategy.

Predictability of Nonremitting Depression After First 2 Weeks of Antidepressant Treatment: A VAST-D Trial Report.

Objective: In this secondary analysis of data from the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, the authors sought to determine the effectiveness of early improvement (or lack thereof) for predicting remission from depression with antidepressant therapy. Methods: This study used data from the VAST-D study, a multisite, randomized, single-blind trial with parallel assignment to one of three medication interventions for 1,522 veterans whose major depressive disorder was unresponsive to at least one course of antidepressant treatment meeting minimal standards for dosage and duration. The authors calculated the positive predictive value (PPV) and negative predictive value (NPV) of early improvement on remission, response, or greater than minimal improvement from depression for various degrees of improvement (10%-50%) on the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C) at 1, 2, 4, and 6 weeks. Results: The end of week 2 of treatment was identified as the best time to evaluate early improvement. The presence of a ≥20% drop from the baseline QIDS-C score by the end of week 2 resulted in a PPV for remission of 38% and an NPV of 93% by week 12. Extending the observational window to week 6 minimally improved NPV (97%). This association did not differ across treatment groups. Conclusions: A lack of early improvement at the end of week 2 of antidepressant therapy can be used to inform clinical decisions on the likelihood of nonremission of depression during the subsequent 10 weeks, even when dosage optimization is incomplete.

Agreement between self and psychiatrist reporting of suicidal ideation at a Veterans Administration psychiatric emergency clinic.

BACKGROUND: With suicide rising in the United States, identifying and preventing suicides is increasingly important. To provide a valuable step toward achieving effective suicide risk assessment, this study examines the agreement between self-report measures and psychiatrist documentation of suicidal ideation and behaviors (SI) at a Veterans Administration (VA) psychiatric emergency clinic. METHODS: A total of 377 veterans presenting at a VA psychiatric emergency clinic completed a self-report survey on SI and other acute risk factors for suicidal behavior. We examined agreement between veterans' self-reported SI and psychiatrists' clinical notes regarding SI. RESULTS: A total of 199 veterans (53%) self-reported SI; 80 psychiatrist notes (21%) indicated SI. Psychiatrists and veterans differed in 44% (164/377) of cases. Among the discordant cases, the veterans' self-report was more severe than the psychiatrists' in 97% of cases. Of the 120 veterans with SI and documented as having no SI by psychiatrists, 31 (26%) reported having a suicide plan and 18 (15%) plan preparations. Findings were similar when controlling for presenting problem, current depression, presence of a standardized suicide risk assessment, psychiatrist training level, past suicide attempt, homelessness, diagnosis of personality, or substance use disorder. CONCLUSIONS: Agreement between veterans' self-reports and psychiatrists' documentation of SI was generally low, with veterans self-reporting SI significantly more often than psychiatrists documented SI in their clinical notes. This suggests that inclusion of a self-report questionnaire provides an additional source of data to complement information gleaned from the clinical interview for a more comprehensive risk assessment, but only if actually examined by the clinician.

Treatment of Complicated Grief in Survivors of Suicide Loss: A HEAL Report.

OBJECTIVE: Suffering associated with complicated grief (CG) is profound. Because suicide loss survivors are susceptible to developing CG, identifying effective treatments for suicide loss survivors with CG is a high priority. This report provides data on the acceptability and effectiveness of antidepressant medication and complicated grief therapy (CGT), a CG-targeted psychotherapy, for suicide loss survivors with CG identified by an Inventory of Complicated Grief score ≥ 30. METHODS: This is a secondary analysis of data collected from March 2010 to September 2014 for a 4-site, double-blind, placebo-controlled randomized trial comparing the effectiveness of antidepressant medication alone or in combination with CGT for participants with CG (score ≥ 30 on the Inventory of Complicated Grief) who were bereaved by suicide (SB; n = 58), accident/homicide (A/H; n = 74), or natural causes (NC; n = 263). Using mode of death as a grouping factor, we evaluated acceptability of treatments by comparing 12-week medication and 16-session CGT completion; we evaluated effectiveness by comparing response at week 20, defined by a score of 1 or 2 on the Complicated Grief Clinical Global Impressions-Improvement scale (CG-CGI-I), and additional secondary response measures. RESULTS: Among participants receiving medication alone, SB medication completion rates (36%) were lower than rates for A/H (54%) and NC (68%; χ² = 11.76, P < .01). SB medication completion rates were much higher for SB individuals receiving CGT (82%; χ² = 12.45, P < .001) than for SB individuals receiving medication alone. CGT completion rates were similar in the 3 groups (SB = 74%, A/H = 64%, NC = 77%; χ² = 2.48, P = .29). For SB participants receiving CGT, CG-CGI-I response rates were substantial (64%), but lower compared to the other groups (A/H = 93%, NC = 84%; χ² = 8.00, P < .05). However, on all other outcomes, changes from baseline for SB participants were comparable to those for A/H and NC participants, including number and severity of grief symptoms, suicidal ideation, and grief-related impairment, avoidance, and maladaptive beliefs. CONCLUSIONS: These results raise concern about the acceptability of medication alone as a treatment for complicated grief in treatment-seeking suicide-bereaved adults. In contrast, CGT is an acceptable and promising treatment for suicide-bereaved individuals with complicated grief. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01179568.

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.

Complicated grief after suicide bereavement and other causes of death.

The authors compared baseline demographic characteristics, clinical features, and grief-related thoughts, feelings, and behaviors of individuals bereaved by suicide, accident/homicide and natural causes participating in a complicated grief (CG) treatment clinical trial. Severity of CG and depression and current depression diagnosis did not vary by loss type. After adjusting for baseline demographic features, time since death and relationship to the deceased, those with CG after suicide had the highest rates of lifetime depression, preloss passive suicidal ideation, self-blaming thoughts, and impaired work and social adjustment. Even among this treatment-seeking sample of research participants with CG, suicide survivors may face unique challenges.

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.

Alcohol use in an academic medical school environment: A UC San Diego Healer Education Assessment and Referral (HEAR) Report.

BACKGROUND: Medical students and physicians in training and in practice are at risk for excessive alcohol use and abuse, potentially impacting the affected individuals as well as their family members, trainees, and patients. However, several roadblocks to care, including stigma, often keep them from seeking treatment. METHODS: We analyzed data from anonymous questionnaires completed by medical students, house staff, and faculty from 2009 to 2014 as part of a depression awareness and suicide prevention program at a state-supported medical school in the United States. The authors explored associations between self-reported "drinking too much" and depression, suicidal ideation, substance use, intense affective states, and mental health treatment. RESULTS: Approximately one-fifth of the respondents reported "drinking too much." "Drinking too much" was associated with more severe depression and impairment, past suicide attempts and current suicidal ideation, intense affective states, and other substance use. Those who were "drinking too much" were more likely than others to accept referrals for mental health treatment through the anonymous interactive screening program, suggesting that this program may be effective in skirting the stigma barrier for accessing mental health care for this at-risk population. CONCLUSIONS: The self-reported prevalence of "drinking too much" among medical students, house staff, and faculty is high and associated with negative mental health outcomes. Targeted, anonymous screenings may identify at-risk individuals and provide mental health care referrals to those in need.

Schizotypy versus openness and intelligence as predictors of creativity.

Schizophrenia-spectrum risk alleles may persist in the population, despite their reproductive costs in individuals with schizophrenia, through the possible creativity benefits of mild schizotypy in non-psychotic relatives. To assess this creativity-benefit model, we measured creativity (using 6 verbal and 8 drawing tasks), schizotypy, Big Five personality traits, and general intelligence in 225 University of New Mexico students. Multiple regression analyses showed that openness and intelligence, but not schizotypy, predicted reliable observer ratings of verbal and drawing creativity. Thus, the 'madness-creativity' link seems mediated by the personality trait of openness, and standard creativity-benefit models seem unlikely to explain schizophrenia's evolutionary persistence.