Efficacy of deep brain stimulation for treatment-resistant depression: systematic review and meta-analysis.

Background: Treatment-resistant depression (TRD) affects about 30% of individuals with major depressive disorder. Deep brain stimulation (DBS) is an investigational intervention for TRD 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 PRISMA guidelines. Seven randomized-controlled trials (n=198) and eight open-label trials (n=77) were included, spanning 2009-2020. 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 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: DBS achieved 47% improvement in long-term depression scale scores, with an estimated time to reach 50% improvement 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 compared to 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: DBS produces significant chronic improvement in symptoms of TRD. The limited sham-controlled data, however, does not demonstrate significant improvement over placebo. Future advancements in stimulation optimization and careful blinding and placebo schemes are important next steps for this therapy.