Background About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression. Methods This Phase 3, double-blind, multicenter study enrolled adults with moderate-to-severe depression and nonresponse to ≥2 antidepressants in the current depression episode. Eligible patients (N = 346) were randomized (1:1:1) to twice-weekly nasal spray treatment (esketamine [56 or 84 mg] or placebo) plus a newly initiated, open-label, oral antidepressant taken daily for 4 weeks. The primary efficacy endpoint was change from baseline to day 28 in the Montgomery-Asberg Depression Rating Scale total score, performed by blinded, remote raters. Based on the predefined statistical testing sequence, esketamine 84 mg/antidepressant had to be significant for esketamine 56 mg/antidepressant to be formally tested. Results Statistical significance was not achieved with esketamine 84 mg/antidepressant compared with antidepressant/placebo (least squares [LS] means difference [95% CI]: –3.2 [–6.88, 0.45]; 2-sided P value = .088). Although esketamine 56 mg/antidepressant could not be formally tested, the LS means difference was –4.1 [–7.67, –0.49] (nominal 2-sided P value = .027). The most common (>20%) adverse events reported for esketamine/antidepressant were nausea, dissociation, dizziness, vertigo, and headache. Conclusions Statistical significance was not achieved for the primary endpoint; nevertheless, the treatment effect (Montgomery-Asberg Depression Rating Scale) for both esketamine/antidepressant groups exceeded what has been considered clinically meaningful for approved antidepressants vs placebo. Safety was similar between esketamine/antidepressant groups and no new dose-related safety concerns were identified. This study provides supportive evidence for the safety and efficacy of esketamine nasal spray as a new, rapid-acting antidepressant for patients with treatment-resistant depression. Trial Registration ClinicalTrials.gov identifier: NCT02417064

The past decade, Belgium has witnessed significant changes in the practice of ECT. The number of facilities providing ECT almost halved adding to the growing expertise of fewer but larger ECT facilities. A possible down side to specialization is a potential diminution of the availability of ECT, requiring adequate referral policies in hospitals without ECT facilities. Although the practice significantly improved, continuous education is needed.

Suicidal behavior constitutes a major public health problem. Based on the stress–diathesis model, biological correlates of a diathesis might help to predict risk after stressor-exposure. Structural changes in cortical and subcortical areas and their connections have increasingly been linked with the diathesis. The current study identified structural network changes associated with a diathesis using a whole-brain approach by examining the structural connectivity between regions in euthymic suicide attempters (SA). In addition, the association between connectivity measures, clinical and genetic characteristics was investigated. We hypothesized that SA showed lower connectivity strength, associated with an increased severity of general clinical characteristics and an elevated expression of short alleles in serotonin polymorphisms. Thirteen euthymic SA were compared with fifteen euthymic non-attempters and seventeen healthy controls (HC). Clinical characteristics and three serotonin-related genetic polymorphisms were assessed. Diffusion MRI together with anatomical scans were administered. Preprocessing was performed using Explore DTI. Whole brain tractography of the diffusion-weighted images was followed by a number of streamlines-weighted network analysis using NBS. The network analysis revealed decreased connectivity strength in SA in the connections between the left olfactory cortex and left anterior cingulate gyrus. Furthermore, SA had increased suicidal ideation, hopelessness and self-reported depression, but did not show any differences for the genetic polymorphisms. Finally, lower connectivity strength between the right calcarine fissure and the left middle occipital gyrus was associated with increased trait anxiety severity (rs = −0.78, p < 0.01) and hopelessness (rs = −0.76, p < 0.01). SA showed differences in white matter network connectivity strength associated with clinical characteristics. Together, these variables could play an important role in predicting suicidal behavior.