Deep brain stimulation of the medial forebrain bundle for treatment-resistant depression - a narrative literature review

Abstract

Purpose: Deep brain stimulation (DBS) is a relatively new and still experimental treatment modality for treatment-resistant depression (TRD). There is preliminary evidence that stimulation of brain reward circuit structures or their connecting white matter bundles may exert an antidepressant effect. The main nucleus of the reward circuit is the nucleus accumbens (NAc), which plays a critical role in reward-seeking behavior, motivation, and addiction. Also, white matter bundles connecting different structures of the reward circuit have been studied clinically as targets for DBS, including the medial forebrain bundle (MFB) - a central component of the mesolimbic dopaminergic reward circuit. This review aims to present the clinical outcomes of MFB DBS for TRD.

Views: The scientific literature was reviewed using the following keywords: 'DBS', 'major depressive disorders', 'TRD', and 'MFB'. The identified studies were assessed on the basis of patient characteristics, clinical outcomes, and adverse events related to DBS. The search revealed five open-label clinical case studies and four case reports reporting the cumulative number of 35 patients treated by MFB DBS for TRD.

Conclusions: The current clinical data of MFB DBS are limited by small sample size and the small number of clinical open-label trials. There is an urgent need for more clinical trials targeting the MFB for TRD. The results obtained in these studies showed a very rapid antidepressant effect observed within one week after the start of stimulation. MFB DBS for TRD should be considered as a last resort treatment due to its invasive character. However, this treatment may be a promising alternative for TRD patients.

Keywords: deep brain stimulation; major depressive disorder; medial forebrain bundle; treatment-resistant depression.

Figure I

Anterior-posterior X-ray of the head, neck, and upper chest region showing the implanted deep brain stimulation system consisting of two intracerebral electrodes (E), connecting wires (CW), and an implantable pulse generator (IPG) for simultaneous stimulation of both hemispheres

Figure II

Axial T2-weighted brain image at the level of the maximal diameter of the red nucleus. The stimulated region is located between the mammillary bodies, the red nucleus, and the most anterior aspect of the subthalamic nucleus. RN – red nucleus, MB – mammillary body, STN – subthalamic nucleus. The white dot indicates the area targeted and containing the superolateral branch of the medial forebrain bundle (slMFB). The utilization of tractography is mandatory in proper targeting of this white matter bundle constituting the neu-roanatomical substrate of the target