Pharmacological and somatic treatment effects on suicide in adults: A systematic review and meta-analysis.

BACKGROUND: Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk. METHODS: A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations. RESULTS: In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, p = .005; k = 12) and compared to placebo/no lithium (OR = .46, p = .009; k = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, p < .001; k = 12), but not compared to active controls (OR = .89, p = .468; k = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, p = .007; k = 7). Associations between suicide death and electroconvulsive therapy (OR = .77, p = .053; k = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, p = .090; k = 6) and antipsychotics in psychotic disorders (OR = .39, p = .069; k = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation. CONCLUSION: Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.

Enfeeblement in Essential Tremor: Development and Validation of a New Psychometric Measure.

INTRODUCTION: Despite a growing body of knowledge regarding essential tremor (ET), past studies have fallen short in capturing the full impact of ET on patients and caregivers. We propose enfeeblement (i.e., having the qualities of being prematurely old, helpless, or debilitated) as a novel clinical outcome measure in ET. Due to the lack of enfeeblement scales for ET in the literature, we developed and validated an enfeeblement scale for ET. METHODS: The Essential Tremor Enfeeblement Survey (ETES) consists of eight 5-point Likert-type scale questions and is designed to be a caregiver-reported outcome. RESULTS: Enfeeblement scores showed a floor effect of 15.3%, no ceiling effects, and demonstrated good overall test-retest reliability (intraclass correlation coefficient = 0.73), favorable internal consistency (Cronbach α coefficient = 0.92) and good convergent validity. CONCLUSION: The ETES has robust properties. Aside from future studies of enfeeblement in ET, enfeeblement should be explored more broadly as a psychometric measure across other neurological disorders.

Banking brains: a pre-mortem "how to" guide to successful donation.

A review of the brain banking literature reveals a primary focus either on the factors that influence the decision to become a future donor or on the brain tissue processing that takes place after the individual has died (i.e., the front-end or back-end processes). What has not been sufficiently detailed, however, is the complex and involved process that takes place after this decision to become a future donor is made yet before post-mortem processing occurs (i.e., the large middle-ground). This generally represents a period of many years during which the brain bank is actively engaged with donors to ensure that valuable clinical information is prospectively collected and that their donation is eventually completed. For the past 15 years, the Essential Tremor Centralized Brain Repository has been actively involved in brain banking, and our experience has provided us valuable insights that may be useful for researchers interested in establishing their own brain banking efforts. In this piece, we fill a gap in the literature by detailing the processes of enrolling participants, creating individualized brain donation plans, collecting clinical information and regularly following-up with donors to update that information, and efficiently coordinating the brain harvest when death finally arrives.

Modulation of Trust in Borderline Personality Disorder by Script-Based Imaginal Exposure to Betrayal.

Interpersonal and trust-related difficulties are central features of borderline personality disorder (BPD). In this study, we applied script-driven betrayal imagery to evoke mistrustful behavior in a social reinforcement learning task. In 21 BPD and 20 healthy control (HC) participants, we compared this approach to the standard confederate paradigm used in research studies. The script-driven imagery evoked a transient increase in negative affect and also decreased trusting behavior to a similar degree in both groups. Across conditions, we also replicated previously reported between-group differences in negative affect (increased in BPD) and task behavior (more sensitive to social cues in BPD). These results support the validity of script-driven imagery as an alternative social task stimulus. This script-driven imagery approach is appealing for clinical research studies on reinforcement learning because it eliminates deception, scales easily, and evokes disorder-specific states of social difficulty.

A pilot randomized controlled trial of ketamine in Borderline Personality Disorder.

This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.

Pharmacological and Somatic Treatment Effects on Suicide in Adults: A Systematic Review and Meta-Analysis.

Background: Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk. Methods: A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations. Results: In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, p = .005; k = 12) and compared to placebo/no lithium (OR = .46, p = .009; k = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, p < .001; k = 12), but not compared to active controls (OR = .89, p = .468; k = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, p = .007; k = 7). Associations between suicide death and electroconvulsive therapy (OR = .77, p = .053; k = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, p = .090; k = 6) and antipsychotics in psychotic disorders (OR = .39, p = .069; k = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation. Conclusion: Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.Reprinted from Depress Anxiety 2022; 39:100-112, with permission from John Wiley and Sons. Copyright © 2022.

Essential Tremor as a "Waste Basket" Diagnosis: Diagnosing Essential Tremor Remains a Challenge.

Introduction: The diagnosis of essential tremor (ET) remains a clinical one, and diagnostic errors are common. We aimed to (1) determine precisely how frequently ET diagnoses are misapplied (i.e., what percentage of patients who have been assigned an "ET" diagnosis actually have another movement disorder), (2) determine which other movement disorders are most often misclassified as "ET," and (3) examine the clinical features that were most associated with diagnostic errors. Methods: One hundred four consecutive patients were included who met the following criteria: (1) initial outpatient evaluation by one of the authors (EDL) between January 2015 and December 2019 and (2) pre-evaluation diagnosis of ET. Data on an extensive number of clinical features were extracted from the electronic medical record. Results: Forty-seven (45.2%) patients received a post-evaluation diagnosis of ET, 29 (27.9%) of dystonia, and 28 (26.9%) of other diagnoses including Parkinson's disease (PD) [6 (5.8%)]. Factors associated with an alternative post-evaluation diagnosis other than ET were pre-evaluation diagnosis made by a non-neurologist, shorter tremor duration, irregular tremor, abnormal limb postures, among others. Discussion: Diagnosing ET remains a challenge, with the diagnosis being over-applied and being used as a "waste basket." More than one-half of the patients who were referred to our clinic with an intake diagnosis of ET were given an alternative post-evaluation diagnosis. While PD was reported to be the most frequently missed diagnosis in a past study, dystonia was most commonly missed in our study. Several clinical features can help to differentiate ET from other tremor disorders.

The "Caring Giver": Emotional Caregiving in the Setting of Essential Tremor.

INTRODUCTION: Essential tremor (ET) is a common neurological disorder associated with functional impairment. Emerging evidence shows that some ET caregivers experience burden, but the unique interpersonal aspects of caregiving in the context of ET have not been fully examined. RESEARCH DESIGN: Open-ended questions were administered to 98 ET care-recipient-caregiver dyads. Responses were analyzed using conventional content analysis. RESULTS: The unique visibility of disability and feelings of embarrassment that occur with ET prompts caregivers to be highly attuned to care-recipient emotions. Providing companionship, promoting independence, and reducing embarrassment are three themes we found that describe the ET caregiving experience. DISCUSSION: Caregiving in ET often goes beyond aiding with activities of daily living; it has a significant emotional component especially in relation to independence and embarrassment. Future studies on caregiving in ET and conditions in which disability is visible should consider using a definition of caregiving that includes emotional caregiving.

Patient Companionship in a Movement Disorders Clinic: Outside Assistance Inside the Office.

Objective: We (1) report whether a companion (i.e., spouse, relative, aide) accompanied our consecutive outpatients with a range of movement disorders, (2) identified the set of patient characteristics that was associated with the need for a visit companion, and (3) characterized the role(s) of these companions during the visit. Our overarching goals were to further understand patient needs and the extent of their support networks, and to enrich the clinician-patient interface. Methods: Two-hundred consecutive patients were enrolled from the Movement Disorders Clinic at Yale School of Medicine. We noted whether patients were accompanied by another person during the visit and documented the role of the visit companion during the encounter. Results: One-hundred-twenty-eight of 200 patients (64.0%) brought a companion, with these being spouses (44.8%), adult children (24.1%) or an aide, nurse or social worker (14.5%). Patients who were unemployed (odds ratio [OR] = 5.32, p = 0.019), had a diagnosis of Parkinson's disease or other Parkinsonian syndromes (OR = 10.61, p = 0.001), or were dependent in any instrumental activities of daily living (iADLs) (OR = 4.99, p = 0.005) or basic activities of daily living (bADLs) (OR = 5.81, p = 0.02), had increased odds of presenting to the clinical visit with a visit companion. Visit companions' main roles involved communication (86.7%) and transportation (84.4%). Conclusion: Visit companions were commonly present during movement disorders outpatient visits-two-thirds of patients were accompanied. A number of factors increased the odds of requiring such a companion by 4- or 5-fold.

Contemporary Outcomes of the Fontan Operation: A Large Single-Institution Cohort.

BACKGROUND: The Fontan procedure is the accepted standard for single-ventricle palliation. The goal of this study was to determine short- and midterm outcomes of patients undergoing a Fontan operation at a single institution and to identify contemporary risk factors for acute and chronic failure. METHODS: All patients undergoing a Fontan operation between 1995 and 2016 were included. Failure was defined as death, transplantation, Fontan takedown or revision, fenestration creation or enlargement, plastic bronchitis, protein-losing enteropathy, or major perioperative reintervention. Multivariable logistic and Cox regression models were used to identify risk factors for acute (perioperative) and chronic failure (after hospital discharge or 30 days postoperatively, or both). RESULTS: The cohort included 610 patients. Median age at surgery was 4 years. Median follow-up was 6.8 years. Trends showed increasing use of extracardiac conduits, nonfenestrated Fontan, and extubation in the operating room. Perioperative mortality was 0.5% (n = 3). Transplant-free survival at 5, 10, and 15 years was 97%, 94%, and 92%, respectively; freedom from failure was 91%, 89%, and 87%, respectively. Extubation in the operating room was associated with lower risk of acute failure (odds ratio, 0.30; 95% confidence interval [CI], 0.11 to 0.87). Independent risk factors for chronic failure included genetic syndrome (hazard ratio [HR], 2.54; 95% CI, 1.11 to 5.83), ventricular dysfunction (HR, 3.86; 95% CI, 1.81 to 8.24), cardiopulmonary bypass time in 30-minute intervals (HR, 1.242; 95% CI, 1.100 to 1.402), and persistent pleural effusions (HR, 4.26; 95% CI, 2.25 to 8.07). Moderate or severe atrioventricular valve regurgitation (HR, 2.61; 95% CI, 1.13 to 6.02) and cardiopulmonary bypass time (HR, 1.22; 95% CI, 1.03 to 1.45) were associated with reduced long-term transplant-free survival. CONCLUSIONS: Contemporary midterm outcomes for Fontan patients are reassuring. Lifelong follow-up is mandatory to determine long-term outcomes and need for additional surgery as patients reach adulthood.

Mid-Term Outcomes in Patients with Congenitally Corrected Transposition of the Great Arteries: A Single Center Experience.

BACKGROUND: Optimal management of patients with congenitally corrected transposition of the great arteries (ccTGA) is unclear. The goal of this study was to compare the outcomes in patients with ccTGA undergoing different management strategies. STUDY DESIGN: Patients with ccTGA believed suitable for biventricular circulation, treated between 1995 and 2016, were included. The cohort was divided into 4 groups: systemic right ventricle (RV) (patients without surgical intervention or with a classic repair), anatomic repair, Fontan palliation, and patients receiving only a pulmonary artery band (PAB) or a shunt. Transplant-free survival from presentation was calculated for each group. RESULTS: The cohort included 97 patients: 45 (46%) systemic RV, 26 (27%) anatomic repair, 9 (9%) Fontan, and 17 (18%) PAB/shunt. Median age at presentation was 2 months (range 0 days to 69 years) and median follow-up was 10 years (1 month to 28 years). At initial presentation, 10 (11%) patients had any RV dysfunction (8 mild, 2 severe), and 16 (18%) patients had moderate or severe tricuspid regurgitation (TR). During the study, 10 (10%) patients died, and 3 (3%) patients underwent transplantation. At last follow-up, 11 (11%) patients were in New York Heart Association class III/IV, 5 (5%) had moderate or severe systemic ventricle dysfunction, and 16 (16%) had moderate or severe systemic atrioventricular valve regurgitation. Transplant-free survivals at 10 years were 93%, 86%, 100%, and 79% for systemic RV, anatomic repair, Fontan palliation, and PAB/shunt, respectively (p = 0.33). On multivariate analysis, only systemic RV dysfunction was associated with a higher risk for death or transplant (p = 0.001). CONCLUSIONS: Transplant-free survival in ccTGA appears to be similar between patients with a systemic RV, anatomic repair, and Fontan procedure. Systemic RV dysfunction is a risk factor for death and transplant.