Background: Deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCC) has shown promise as an intervention for patients with chronic, unremitting depression (TRD). To test the safety and efficacy of DBS for TRD, a prospective, randomized, sham-controlled trial was conducted. Methods: Participants with TRD were implanted with a DBS system targeting bilateral SCC white matter and randomized to six months of active versus sham DBS followed by six months open-label SCC DBS. The primary outcome was response rate at the end of the six-month double-blind phase. Response was defined as a 40% or greater reduction in depression severity from baseline. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients continued to be followed for up to 24 months. Findings: Prior to the futility analysis, 90 participants were randomized to active (N=60) versus sham (N=30) stimulation. Both groups showed improvement, but there was no statistically significant difference in response rate during the double-blind, sham-controlled phase. Participants continued to improve during the six months open-label phase. Long-term response and remission rates for all participants receiving active DBS open-label were, respectively, 40% and 19% at 12 months, 51%

Multiple randomized controlled trials and published literature have supported the safety and efficacy of rTMS antidepressant therapy. These consensus recommendations, developed by the NNDC rTMS Task Group and APA CoR Task Force on Novel Biomarkers and Treatments, provide comprehensive information for the safe and effective clinical application of rTMS in the treatment of MDD.

Each electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.

The effects of major depressive disorder (MDD) on neurocognitive function remain poorly understood. Results from published studies vary widely in terms of methodological factors, and very little is known about the effects of depression severity and other clinical characteristics on neurocognitive function. The purpose of this review was to synthesize prior research findings regarding neurocognitive functioning in patients with MDD and varying levels of depression severity and to provide recommendations for future directions. Overall, this review suggests that MDD has been inconsistently associated with neurocognitive functioning and there is limited understanding regarding the relationship between depression severity and neurocognitive sequelae. There was much heterogeneity on depression severity-related factors across studies assessing neurocognitive function in MDD, as well as substantial variability in the consideration of depression severity among studies, which suggests a need to further explore this important issue.

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Previous animal models and structural imaging investigations have linked hippocampal neuroplasticity to electroconvulsive therapy (ECT) response, but the relationship between changes in hippocampal volume and temporal coherence in the context of ECT response is unknown. We hypothesized that ECT response would increase both hippocampal resting-state functional magnetic resonance imaging connectivity and hippocampal volumes. Patients with major depressive disorder (n=19) were scanned before and after the ECT series. Healthy, demographically matched comparisons (n=20) were scanned at one-time interval. Longitudinal changes in functional connectivity of hippocampal regions and volumes of hippocampal subfields were compared with reductions in ratings of depressive symptoms. Right hippocampal connectivity increased (normalized) after the ECT series and correlated with depressive symptom reduction. Similarly, the volumes of the right hippocampal cornu ammonis (CA2/3), dentate gyrus and subiculum regions increased, but the hippocampal subfields were unchanged relative to the comparison group. Connectivity changes were not evident in the left hippocampus, and volume changes were limited to the left CA2/3 subfields. The laterality of the right hippocampal functional connectivity and volume increases may be related to stimulus delivery method, which was predominately right unilateral in this investigation. The findings suggested that increased hippocampal functional connectivity and volumes may be biomarkers for ECT response.

Psychomotor retardation is a long established component of depression that can have significant clinical and therapeutic implications for treatment. Due to its negative impact on overall function in depressed patients, we review its biological correlates, optimal methods of measurement, and relevance in the context of therapeutic interventions. The aim of the paper is to provide a synthesis of the literature on psychomotor retardation in depression with the goal of enhanced awareness for clinicians and researchers. Increased knowledge and understanding of psychomotor retardation in major depressive disorder may lead to further research and better informed diagnosis in regards to psychomotor retardation. Manifestations of psychomotor retardation include slowed speech, decreased movement, and impaired cognitive function. It is common in patients with melancholic depression and those with psychotic features. Biological correlates may include abnormalities in the basal ganglia and dopaminergic pathways. Neurophysiologic tools such as neuroimaging and transcranial magnetic stimulation may play a role in the study of this symptom in the future. At present, there are three objective scales to evaluate psychomotor retardation severity. Studies examining the impact of psychomotor retardation on clinical outcome have found differential results. However, available evidence suggests that depressed patients with psychomotor retardation may respond well to electroconvulsive therapy (ECT). Current literature regarding antidepressants is inconclusive, though tricyclic antidepressants may be considered for treatment of patients with psychomotor retardation. Future work examining this objective aspect of major depressive disorder (MDD) is essential. This could further elucidate the biological underpinnings of depression and optimize its treatment.

Objective-This study assessed the incidence, severity, and course of expressed suicidal intent in depressed patients who were treated with ECT. The data are from the first phase of an ongoing, collaborative multicenter study, the overall aim of which was to compare continuation ECT with pharmacotherapy in the prevention of relapse after a successful course of ECT.Method-Suicidal intent, as expressed by patients during an interview, was scored at baseline and before each ECT session with item 3 on the 24-item Hamilton Depression Rating Scale in 444 patients with unipolar depression.Results-One hundred thirty-one patients (29.5%) reported suicidal thoughts and acts (score of 3 or 4) at baseline. Scores decreased to 0 after 1 week (three ECT sessions) in 38.2% of the patients, after 2 weeks (six ECT sessions) in 61.1%, and in 80.9% at the end of the course of treatment.Conclusions-Expressed suicidal intent in depressed patients was rapidly relieved with ECT. Evidence-based treatment algorithms for major depressive mood disorders should include dichotomization according to suicide risk, as assessed by interview. For patients at risk, ECT should be considered earlier than at its conventional "last resort" position.Suicide and suicide attempts are risks of the major psychiatric illnesses, with mortality rates markedly higher than for the general population (1). A lifetime risk of 15% for suicide was the conclusion of a meta-analysis of hospitalized patients by Guze and Robins (2). A reanalysis of studies of suicide in affective illness in three groups of patients-outpatients, inpatients, and suicidal patients-found a risk of those ever hospitalized of 8.6% (3). Other studies confirmed the risk of suicide to be particularly high in hospitalized depressed patients (4-6). Profound hopelessness, hypochondriacal ruminations or delusions, and thoughts of suicide or self-harm during depression predict future suicide (7).Antidepressant medications are the principal agents used to treat affective disorders today. Their impact on suicide risk is not well defined, however, and they are generally viewed as less effective than ECT in relieving depression and suicidal thoughts. Hordern et al. (8) reported no suicides at the 6-month follow-up in 34 women treated with ECT but found two in the 84 patients treated with antidepressants (2.4%). Avery and Winokur (9) suicidal behavior in the 6 months following the treatment of depression in 519 patients. Suicide attempts were recorded in 0.8% of the ECT patients compared to 4.2% of those who had received "adequate" and 7% "inadequate" antidepressant medication treatment. Khan et al. (10) found antidepressant drugs to be no more effective than placebo in reducing suicide rates in seriously ill depressed patients.The experience with ECT is also unclear. A comparison of the frequency of suicides in different decades found decreased rates when ECT was the dominant treatment for mental illness (11). An examination of the records of 1,397 completed suicides in Finland within a 12-m...