More effective treatments are needed for major depressive disorder (MDD), which is common, disabling, and costly.^1-4 After acute-phase pharmacotherapy, psychotherapy, or both, most depressed patients either do not improve or achieve only partial symptomatic improvement.^5-9 In addition to efficacy and durability concerns, pharmacologic and other somatic treatments often have treatment-limiting adverse effects (eg, sexual dysfunction).^10-17 Nonetheless, across all of medicine, antidepressants are the most commonly prescribed class of medications.¹⁸

FOR DECADES there has been a controversy concerning the use of right unilateral (RUL) or bilateral (BL) electroconvulsive therapy (ECT) in major depression.¹ It has been established that RUL ECT causes less severe cognitive adverse effects than BL ECT.^2-6 However, despite 40 comparative trials, the relative efficacy of both RUL and BL ECT remains uncertain.^1,7-9 When efficacy differences have been found, they consistently favored BL ECT.^10-12 Most patients in the United States receive BL treatment. Farah and McCall¹³ conducted a survey of US ECT practitioners and found that 52% initiated ECT with the BL placement. We recently conducted a survey of ECT directors at 59 facilities in the tristate New York metropolitan area (H.A.S. and J.P., unpublished data, January 1, 1997, to July 1, 1997). The mean percentage of patients receiving BL ECT was 79%.

To provide expert recommendations for the safe and effective application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). Participants included a group of 17 expert clinicians and researchers with expertise in the clinical application of rTMS, representing both the National Network of Depression Centers (NNDC) rTMS Task Group and the American Psychiatric Association Council on Research (APA CoR) Task Force on Novel Biomarkers and Treatments. The consensus statement is based on a review of extensive literature from 2 databases (OvidSP MEDLINE and PsycINFO) searched from 1990 through 2016. The search terms included variants of major depressive disorder and transcranial magnetic stimulation. The results were limited to articles written in English that focused on adult populations. Of the approximately 1,500 retrieved studies, a total of 118 publications were included in the consensus statement and were supplemented with expert opinion to achieve consensus recommendations on key issues surrounding the administration of rTMS for MDD in clinical practice settings. In cases in which the research evidence was equivocal or unclear, a consensus decision on how rTMS should be administered was reached by the authors of this article and is denoted in the article as "expert opinion." 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.

Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. 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 were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. Abbott (previously St Jude Medical).