Efficacy of Deep Brain Stimulation for Treatment-Resistant Depression: Systematic Review and Meta-Analysis.

Background: Treatment-resistant depression affects about 30% of individuals with major depressive disorder. Deep brain stimulation is an investigational intervention for treatment-resistant depression with varied results. We undertook this meta-analysis to synthesize outcome data across trial designs, anatomical targets, and institutions to better establish efficacy and side-effect profiles.

Methods: We conducted a systematic PubMed review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven randomized controlled trials (n = 198) and 8 open-label trials (n = 77) were included spanning 2009 to 2020. Outcome measures included Hamilton Depression Rating Scale or Montgomery-Åsberg Depression Rating Scale scores, as well as response and remission rates over time. Outcomes were tracked at the last follow-up and quantified as a time course using model-based network meta-analysis. Linear mixed models were fit to individual patient data to identify covariates.

Results: Deep brain stimulation achieved 47% improvement in long-term depression scale scores, with an estimated time to reach 50% improvement of around 23 months. There were no significant subgroup effects of stimulation target, time of last follow-up, sex, age of disease onset, or duration of disease, but open-label trials showed significantly greater treatment effects than randomized controlled trials. Long-term (12-60 month) response and remission rates were 48% and 35%, respectively. The time course of improvement with active stimulation could not be adequately distinguished from that with sham stimulation, when available.

Conclusions: Deep brain stimulation produces significant chronic improvement in symptoms of treatment-resistant depression. However, the limited sham-controlled data do not demonstrate significant improvement over placebo. Future advancements in stimulation optimization and careful blinding and placebo schemes are important next steps for this therapy.