In addition to obtaining a history of suicidal behavior, clinicians may find it useful to assess patients' current level of pessimism, aggressive/impulsive traits, and comorbidity with substance use disorders, including nicotine-related disorders, to help identify patients at risk for suicidal behavior after major depression. Interventions such as aggressive pharmacotherapeutic prophylaxis to prevent relapse or recurrence of depressive symptoms may protect such at-risk individuals from future suicidal behavior.

Religious affiliation is associated with less suicidal behavior in depressed inpatients. After other factors were controlled, it was found that greater moral objections to suicide and lower aggression level in religiously affiliated subjects may function as protective factors against suicide attempts. Further study about the influence of religious affiliation on aggressive behavior and how moral objections can reduce the probability of acting on suicidal thoughts may offer new therapeutic strategies in suicide prevention.

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. Method This randomized clinical trial tested the effect of adjunctive sub-anesthetic intravenous ketamine on clinically significant suicidal ideation in major depressive disorder (MDD). Adults (N=80) with current MDD and score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomized to ketamine or midazolam infusion. The primary outcome was Day 1 SSI score (24 hours post-infusion). Other outcomes included global depression and adverse effects. Results Reduction of SSI score was 4.96 points greater after ketamine compared with midazolam at Day 1 (95% confidence interval (CI)=2.33 to 7.59; p=0.0003; Cohen’s d=0.75). Proportion of responders (≥50% reduction in SSI) at Day 1 was 55% after ketamine and 30% after midazolam (OR=2.85 (95% CI=1.14 to 7.15); p=0.0237; NNT=4.00). Improvement in the Profile of Mood States (POMS) depression subscale was greater at Day 1 compared with midazolam treatment (Estimate=7.65 (95% CI=1.36 to 13.94), df=75, t=2.42, p=0.0178), and this effect mediated 33.6% of ketamine’s effect on SSI score. Side effects were short-lived. Benefit was sustained for up to six weeks with clinical pharmacotherapy. Conclusions Adjunctive ketamine demonstrated greater reduction of clinically significant suicidal ideation in depressed patients within 24 hours compared to midazolam, partially independent of antidepressant effect. Research is needed to understand ketamine’s mechanism of action and to develop safe, longer-term treatment.

Background Inflammation has been linked to depression and suicide risk. One inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP). Recent data suggest that KYN increases in cerebrospinal fluid (CSF) are associated with depressive symptoms secondary to immune activation. KYN may alter dopaminergic and glutamatergic tone, thereby contributing to increased arousal, agitation and impulsivity - important risk factors in suicide. We hypothesized that patients with Major Depressive Disorder (MDD) and a history of suicide attempt would have higher levels of KYN than depressed nonattempters, who in turn would have higher levels than healthy volunteers. Methods Plasma KYN, TRP, and neopterin were assayed by high performance liquid chromatography in three groups: healthy volunteers (n=31) and patients with MDD with (n=14) and without (n=16) history of suicide attempt. Analysis of variance tested for group differences in KYN levels. Results KYN levels differed across groups (F=4.03, df=(2,58), p=0.023): a priori planned contrasts showed that KYN was higher in the MDD suicide attempter subgroup compared with MDD non-attempters (t=2.105, df=58, p=0.040), who did not differ from healthy volunteers (t=0.418, df=58, p=0.677). In post-hoc testing, KYN but not TRP was associated with attempt status, and only suicide attempters exhibited a positive correlation of the cytokine activation marker neopterin with the KYN:TRP ratio, suggesting that KYN production may be influenced by inflammatory processes among suicide attempters. Conclusions These preliminary results suggest that KYN and related molecular pathways may be implicated in the pathophysiology of suicidal behavior.