Objective:Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients ...with low levels of suicidal ideation. The authors tested the acute effect of adjunctive subanesthetic intravenous ketamine on clinically significant suicidal ideation in patients with major depressive disorder.Method:In a randomized clinical trial, adults (N=80) with current major depressive disorder and a score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomly assigned to receive ketamine or midazolam infusion. The primary outcome measure was SSI score 24 hours after infusion (at day 1). Results:The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen’s d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine’s effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up.Conclusions:Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect.
IMPORTANCE: Suicidal behavior is a major public health problem in the United States. The suicide rate has steadily increased over the past 2 decades; middle-aged men and military veterans are at ...particularly high risk. There is a dearth of empirically supported brief intervention strategies to address this problem in health care settings generally and particularly in emergency departments (EDs), where many suicidal patients present for care. OBJECTIVE: To determine whether the Safety Planning Intervention (SPI), administered in EDs with follow-up contact for suicidal patients, was associated with reduced suicidal behavior and improved outpatient treatment engagement in the 6 months following discharge, an established high-risk period. DESIGN, SETTING, AND PARTICIPANTS: Cohort comparison design with 6-month follow-up at 9 EDs (5 intervention sites and 4 control sites) in Veterans Health Administration hospital EDs. Patients were eligible for the study if they were 18 years or older, had an ED visit for a suicide-related concern, had inpatient hospitalization not clinically indicated, and were able to read English. Data were collected between 2010 and 2015; data were analyzed between 2016 and 2018. INTERVENTIONS: The intervention combines SPI and telephone follow-up. The SPI was defined as a brief clinical intervention that combined evidence-based strategies to reduce suicidal behavior through a prioritized list of coping skills and strategies. In telephone follow-up, patients were contacted at least 2 times to monitor suicide risk, review and revise the SPI, and support treatment engagement. MAIN OUTCOMES AND MEASURES: Suicidal behavior and behavioral health outpatient services extracted from medical records for 6 months following ED discharge. RESULTS: Of the 1640 total patients, 1186 were in the intervention group and 454 were in the comparison group. Patients in the intervention group had a mean (SD) age of 47.15 (14.89) years and 88.5% were men (n = 1050); patients in the comparison group had a mean (SD) age of 49.38 (14.47) years and 88.1% were men (n = 400). Patients in the SPI+ condition were less likely to engage in suicidal behavior (n = 36 of 1186; 3.03%) than those receiving usual care (n = 24 of 454; 5.29%) during the 6-month follow-up period. The SPI+ was associated with 45% fewer suicidal behaviors, approximately halving the odds of suicidal behavior over 6 months (odds ratio, 0.56; 95% CI, 0.33-0.95, P = .03). Intervention patients had more than double the odds of attending at least 1 outpatient mental health visit (odds ratio, 2.06; 95% CI, 1.57-2.71; P < .001). CONCLUSIONS AND RELEVANCE: This large-scale cohort comparison study found that SPI+ was associated with a reduction in suicidal behavior and increased treatment engagement among suicidal patients following ED discharge and may be a valuable clinical tool in health care settings.
Suicidal behavior (SB) can be impulsive or methodical; violent or not; follow a stressor or no obvious precipitant. This study tested whether childhood trauma, affective lability, and aggressive and ...impulsive traits predicted greater SI variability. We also assessed whether affective lability, aggressive or impulsive traits explain childhood trauma's effects on SI variability and whether those with highly variable SI respond to stressful events with increases in SI. Finally, we assessed variable SI's trajectory over 2 years. Depressed participants (n = 51) had ecological momentary assessments (EMA) over 7 days at baseline, 3, 6, 12, 18, and 24 months. SI variability was assessed using the square Root of the Mean Square of Successive Deviations. Mixed Effects Models were fit as appropriate. Childhood trauma was associated with subsequent aggression. Physical abuse predicted both aggression and affective lability as well as SI variability, but not impulsivity. In two-predictor models, physical abuse's effect on SI variability was no longer significant, when controlling for the effect of higher aggression and impulsivity. Those with high SI variability exhibited greater increases in SI after stressors compared with those with less variability. We did not find that SI variability changed over time, suggesting it might be trait-like, at least over 2 years. Variable SI predisposes to marked SI increases after stressful events and may be a trait increasing risk for impulsive SB, at least over 2 years.
This clinical viewpoint article aims to draw attention to a yet unexplored factor influencing suicidal behavior: age of onset of suicidal behavior. To tackle the substantial heterogeneity among ...depressed older attempters, we suggest consideration of at least two distinct pathways to suicidal behavior in late life based on when the first suicidal crisis occurred. Specifically, we discuss the current state of research and the rationale behind the suggested early-late-onset categorization of late-life suicidal behavior. We summarize available evidence so far on early-onset and late-onset attempters, and the potential heterogeneity in the interplay of risk/precipitating factors. Certain risk factors for suicide, such as impulsivity and borderline traits, decrease with age, while memory and broader cognitive impairments increase with age. Research indicates that familial/social exposure to suicidal behavior, childhood trauma, impulsivity, maladaptive personality traits, longstanding interpersonal difficulties, and legal problems are found predominantly in attempters experiencing their first suicidal crisis between youth and early midlife. In contrast, dementia prodrome is one of the most promising but understudied candidates for late-onset suicide risk, especially in the context of other risk factors. Moreover, personality traits conferring increased vulnerability to late-onset suicidal behavior (such as high conscientiousness) are not the same as ones classically identified in younger attempters and in older suicide attempters who have early-onset suicidal behavior (such as neuroticism and Cluster B traits). We discuss methodological points about studying age of onset of suicidal behavior, outline clinical implications, share ideas for future directions, and call for research on this understudied topic.
Individuals who have lost a loved one to suicide are at increased risk for developing complicated grief (CG). It is unclear why only a subgroup of bereaved develops pathological forms of grief. ...Vulnerability may be related to the ability to regulate attention toward reminders of the deceased during the acute phase of grief. Using a longitudinal design, we determined whether loss-related attentional bias during acute grief predicts grief severity one year later.
Thirty-seven participants grieving a first-degree relative or partner to suicide in the prior 6 months performed an emotional Stroop task using words related to the deceased, a living attachment figure, living non-attachment figure, and color congruent Stroop to quantify related attentional bias during the acute grief period. Clinical interviews were conducted at baseline (N = 37) and one year later (N = 35).
Participants showed greater attentional bias to deceased-related word trials compared with living attachment, non-attachment, and congruent trials, controlling for age, time since loss, depression, and psychiatric medication. A greater reduction in grief severity over time was associated with more deceased-related attentional bias at baseline. Self-reported grief avoidance was related to deceased-related attentional bias, with lower avoidance scores associated with greater bias.
Lack of non-suicide grief control and small sample size.
Less deceased-related bias following the loss may hinder the transition from acute to integrated grief and result in poorer grief trajectories.
•It is unknown why only a subgroup of suicide bereaved develop pathological grief.•Attention regulation in acute grief may be a cognitive marker of grief trajectories.•Deceased-related attentional bias predicted grief outcomes one year later.•Grief-related avoidance in acute grief may indicate poorer grief trajectories.
Our group reported previously a comparable overall antisuicidal effect of lithium and valproate in bipolar patients. We investigated factors associated with higher antisuicidal efficacy of lithium in ...older individuals.
The age-related antisuicidal effect of lithium and valproate was compared in ninety-four (n = 94) high-risk bipolar suicide attempters who participated in a 2.5-year randomized, double-blind trial.
Age significantly moderated the effect of lithium vs. valproate on the risk of suicide event during the study (z = −1.98, p = 0.049). We found that those who were 42 years or older (above the 75th percentile), and on lithium had significantly lower risk of suicidal behavior than older patients on valproate (>42y) or younger (<42 y) patients on either medication (interaction HR = 0.09, 95%CI: 0.01–0.89, z = −2.07, p = 0.039). This difference in risk differences was not explained away by age-related differences in the proportion of participants with bipolar II disorder (Fisher's test p = 0.020) or higher lethality of past suicide attempts in younger participants (Wilcoxon test p = 0.024); neither was there any correlation with age in the longitudinally measured blood lithium levels (t = 1.04, df = 36, p = 0.307) or valproate levels (t = −0.50, df = 41, p = 0.621).
Besides the fact that this is a secondary analysis, a limitation is that the study is not powered to detect suicide deaths or suicide attempts.
Bipolar patients randomized to lithium and older than 42 years had less suicidal behavior compared to same aged patients on valproate or younger patients (<42 y) on either medication. This effect was independent of clinical and sociodemographic characteristics.
•Antisuicidal effect of lithium appears to be stronger in bipolar patients ≥42 years•Suicide attempt risk in this patient group was lower than in other three groups•This age-effect was independent of patients' clinical and demographic characteristics
There is a public health need for improved suicide risk assessment tools. This pilot methodology study compared the assay sensitivity of computerized adaptive tests (CAT) of depression and suicidal ...ideation vs. traditional ratings in a randomized trial subgroup. The last 20 persons to enroll in a published ketamine trial in suicidal depression were studied. This subgroup received traditional and CAT ratings at baseline, 24 h post-infusion and follow-up week 2, 4, and 6: Hamilton Depression Rating Scale, Beck Depression Inventory, and Beck Scale for Suicidal Ideation vs. the CAT-Depression Inventory and CAT-Suicide Scale. Results showed larger effect sizes (ES) for CAT compared with traditional clinician-rated and self-report scales. Coefficients of variation for baseline measurements were lower for CAT compared with traditional scales. This is the first study to show that CAT may have greater assay sensitivity for treatment effects, particularly for suicidal ideation, compared with traditional clinician-rated and non-adaptive self-rated scales in a randomized trial. The findings suggest CAT can enable quick long-term follow-up assessments via cellphone, tablet, or computer while minimizing response bias due to repeated measurement of the same symptom items.
www.ClinicalTrials.gov, identifier: NCT01700829.
•Race-ethnicity groups did not differ in age, sex, income, or depressive episode number.•Longer delays from first major depressive episode to antidepressant medication for non-Hispanic Black and ...Hispanic (any race) participants.•Non-Hispanic Black and Hispanic (any race) participants have lower rates of lifetime depression treatment.
Time from first DSM4 major depressive episode (MDE) until treatment in the community was compared across racial/ethnic groups. This secondary analysis used structured baseline data from a depression research clinic (N = 260). Chi-square and survival analyses compared rates and delays to antidepressant medication and psychotherapy. Non-Hispanic Black and Hispanic (any race) participants had lower rates of both antidepressant medication and psychotherapy and longer delays to antidepressant medication compared with non-Hispanic White participants. The results underscore the need to reduce these disparities.
We sought to explore relationships of acute dissociative effects of intravenous ketamine with change in depression and suicidal ideation and with plasma metabolite levels in a randomized, ...midazolam-controlled trial.
Data from a completed trial in suicidal, depressed participants (n = 40) randomly assigned to ketamine was used to examine relationships between ketamine treatment-emergent dissociative and psychotomimetic symptoms with pre/post-infusion changes in suicidal ideation and depression severity. Nonparametric correlational statistics were used. These methods were also used to explore associations between dissociative or psychotomimetic symptoms and blood levels of ketamine and metabolites in a subset of participants (n = 28) who provided blood samples immediately post-infusion.
Neither acute dissociative nor psychotomimetic effects of ketamine were associated with changes in suicidal ideation or depressive symptoms from pre- to post-infusion. Norketamine had a trend-level, moderate inverse correlation with dissociative symptoms on Day 1 post-injection (P = .064; P =.013 removing 1 outlier). Dehydronorketamine correlated with Clinician-Administered Dissociative States Scale scores at 40 minutes (P = .034), 230 minutes (P = .014), and Day 1 (P = .012).
We did not find evidence that ketamine's acute, transient dissociative, or psychotomimetic effects are associated with its antidepressant or anti-suicidal ideation actions. The correlation of higher plasma norketamine with lower dissociative symptoms on Day 1 post-treatment suggests dissociation may be more an effect of the parent drug.
Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide ...risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.
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