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.

Background Many patients with major depressive disorder (MDD) who experience full symptomatic remission after antidepressant treatment still have residual depressive symptoms. We describe the types and frequency of residual depressive symptoms and their relationship to subsequent depressive relapse after treatment with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method Participants in primary (n = 18) and psychiatric (n = 23) practice settings were openly treated with citalopram using measurement-based care for up to 14 weeks and follow-up for up to 1 year. We assessed 943 (32.8% of 2876) participants who met criteria for remission to determine the proportions with individual residual symptoms and any of the nine DSM-IV criterion symptom domains to define a major depressive episode. At each visit, the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16) and the self-report Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale were used to assessed depressive symptoms and side-effects respectively. Results More than 90% of remitters had at least one residual depressive symptom (median = 3). The most common were weight increase (71.3%) and mid-nocturnal insomnia (54.9 %). The most common residual symptom domains were sleep disturbance (71.7%) and appetite/weight disturbance (35.9 %). Those who remitted before 6 weeks had fewer residual symptoms at study exit than did later remitters. Residual sleep disturbance did not predict relapse during follow-up. Having a greater number of residual symptom domains was associated with a higher probability of relapse. Conclusions Patients with remission of MDD after treatment with citalopram continue to experience selected residual depressive symptoms, which increase the risk of relapse.

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.

This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.

Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22-68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p50.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p50.013; remission: 32.6 vs. 14.6%, p50.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment.

This open pilot study of vagus nerve stimulation (VNS ™ ) in 60 patients with treatment-resistant major depressive episodes (MDEs)

Neither medication combination outperformed monotherapy. The combination of extended-release venlafaxine plus mirtazapine may have a greater risk of adverse events.