Deep Brain Stimulation of the Medial Forebrain Bundle for Treatment-Resistant Depression: A Systematic Review Focused on the Long-Term Antidepressive Effect

Luigi Gianmaria Remore; Meskerem Tolossa; Wexin Wei; Mohammad Karnib; Evangelia Tsolaki; Ziad Rifi; Ausaf Ahmad Bari

doi:10.1016/j.neurom.2023.03.011

Deep Brain Stimulation of the Medial Forebrain Bundle for Treatment-Resistant Depression: A Systematic Review Focused on the Long-Term Antidepressive Effect

Neuromodulation. 2023 Apr 26:S1094-7159(23)00144-7. doi: 10.1016/j.neurom.2023.03.011. Online ahead of print.

Authors

Luigi Gianmaria Remore¹, Meskerem Tolossa², Wexin Wei², Mohammad Karnib³, Evangelia Tsolaki², Ziad Rifi³, Ausaf Ahmad Bari⁴

Affiliations

¹ Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA; University of Milan "La Statale," Milan, Italy. Electronic address: luigigianmaria.remore@gmail.com.
² Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA.
³ University of California Los Angeles, Los Angeles, CA, USA.
⁴ Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

PMID: 37115122
DOI: 10.1016/j.neurom.2023.03.011

Abstract

Objective: Major depression affects millions of people worldwide and has important social and economic consequences. Since up to 30% of patients do not respond to several lines of antidepressive drugs, deep brain stimulation (DBS) has been evaluated for the management of treatment-resistant depression (TRD). The superolateral branch of the medial forebrain bundle (slMFB) appears as a "hypothesis-driven target" because of its role in the reward-seeking system, which is dysfunctional in depression. Although initial results of slMFB-DBS from open-label studies were promising and characterized by a rapid clinical response, long-term outcomes of neurostimulation for TRD deserve particular attention. Therefore, we performed a systematic review focused on the long-term outcome of slMFB-DBS.

Materials and methods: A literature search using Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was conducted to identify all studies reporting changes in depression scores after one-year follow-up and beyond. Patient, disease, surgical, and outcome data were extracted for statistical analysis. The Montgomery-Åsberg Depression Rating Scale (ΔMADRS) was used as the clinical outcome, defined as percentage reduction from baseline to follow-up evaluation. Responders' and remitters' rates were also calculated.

Results: From 56 studies screened for review, six studies comprising 34 patients met the inclusion criteria and were analyzed. After one year of active stimulation, ΔMADRS was 60.7% ± 4%; responders' and remitters' rates were 83.8% and 61.5%, respectively. At the last follow-up, four to five years after the implantation, ΔMADRS reached 74.7% ± 4.6%. The most common side effects were stimulation related and reversible with parameter adjustments.

Conclusions: slMFB-DBS appears to have a strong antidepressive effect that increases over the years. Nevertheless, to date, the overall number of patients receiving implantations is limited, and the slMFB-DBS surgical technique seems to have an important impact on the clinical outcome. Further multicentric studies in a larger population are needed to confirm slMFB-DBS clinical outcomes.

Keywords: Deep brain stimulation; depression; dopamine; medial forebrain bundle; reward-seeking system.

Publication types

Review