Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression

Abstract

Major depressive disorder (MDD) is a leading cause of disability and a significant cause of mortality worldwide. Approximately 30–40% of patients fail to achieve clinical remission with available pharmacological treatments, a clinical course termed treatment-resistant depression (TRD). Numerous studies have investigated deep brain stimulation (DBS) as a therapy for TRD. We performed a meta-analysis to determine efficacy and a meta-regression to compare stimulation targets. We identified and screened 1397 studies. We included 125 citations in the qualitative review and considered 26 for quantitative analysis. Only blinded studies that compared active DBS to sham stimulation (k = 12) were included in the meta-analysis. The random-effects model supported the efficacy of DBS for TRD (standardized mean difference = −0.75, <0 favors active stimulation; p = 0.0001). The meta-regression did not demonstrate a statistically significant difference between stimulation targets (p = 0.45). While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this meta-analysis reveals a significant effect of DBS for the treatment of TRD. Additionally, the majority of trials have demonstrated the safety and efficacy of DBS for this indication. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including electrode placement technique, patient selection, and long-term follow-up is essential for future trial design.

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies

“…A failure to identify and treat depression can have profound negative public health impacts such as hospitalizations, inter-personal issues, lack of productivity, and suicide. After early randomized controlled trials failed to show improvement, it is now becoming increasingly evident that DBS can be useful for treatment resistant depression, and several studies are showing promise ( Holtzheimer et al, 2017 ; Hitti et al, 2020 ; van der Wal et al, 2020 ) Bergfeld, 2020 ). Stimulation of the subgenual cingulate has been shown to produce clinical benefits in patients with treatment resistant depression ( Mayberg et al, 2005 ).…”

Risk Assessment of Electroconvulsive Therapy in Clinical Routine: A 3-Year Analysis of Life-Threatening Events in More Than 3,000 Treatment Sessions

“…The latter include repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and magnetic seizure therapy (MST). All of them have shown to be effective treatment approaches, rTMS ( Brunoni et al, 2017 ; Sonmez et al, 2019 ; De Risio et al, 2020 ), VNS ( Bottomley et al, 2019 ), and tDCS ( Fregni et al, 2021 ) with consistent effects but moderate effect sizes, DBS ( Hitti et al, 2020 ) and MST ( Weissman et al, 2020 ) with promising and positive results in rather small treatment groups, and VNS and DBS being invasive techniques, which require a neurosurgical procedure. Network meta-analytic estimates of non-surgical brain stimulation revealed ECT as the by far most effective treatment for depression with a bitemporal ECT odds ratio of 8.91, high dose right unilateral ECT 7.27, and lower effect sizes of priming rTMS 6.02, MST 5.55, bilateral rTMS 4.92, bilateral theta burst stimulation 4.44, low-frequency right rTMS 3.65, intermittent theta burst stimulation 3.20, high-frequency left rTMS 3.17, and tDCS 2.65 ( Mutz et al, 2019 ).…”

Special Issue: Trends in Clinical Deep Brain Stimulation

“…Unfortunately, recent randomized controlled trials show disappointing results of DBS for treatment-resistant depression (TRD). Contrary to these findings, the meta-analysis conducted by Hitti et al shows that DBS is an effective treatment for TRD [ 1 ]. This promising finding should serve as an encouragement for future studies to optimize patient selection, stimulation settings and target selection.…”