Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression

- Deep brain stimulation of the medial forebrain bundle is a target for depression.
- Our study aims to replicate the only report at this target describing rapid effects.
- Sham stimulation did not result in significant mood changes.
- 3 of 4 patients had >50% decrease in depression scores 7 days post-stimulation.
- 66% of patients have sustained anti-depressant response at 26 weeks post onset.

BackgroundTreatment resistant depression (TRD) is a serious, disabling disease. Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB), as proposed by Schlaepfer et al. (2013), has led to rapid anti-depressant response but has not been replicated.MethodsIn this interim analysis of an ongoing pilot study of ten subjects, we assessed the efficacy of MFB-DBS in a cohort of four TRD patients over a 52-week period using the Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary assessment tool. Implanted patients entered a 4-week single-blinded sham stimulation period prior to stimulation initiation. Deterministic fiber tracking analysis was performed to compare modulated fiber tracts between patients.ResultsIntraoperatively, responder patients displayed immediate increased signs of energy and motivation upon stimulation at target. There was no significant mean change in mood during sham stimulation phase. Three of 4 patients had >50% decrease in MADRS scores at 7 days post-stimulation initiation relative to baseline. One patient withdrew from study participation. At 26 weeks, two of 3 remaining patients continue to have >80% decrease in MADRS scores. One patient failed to have response; evaluation of modulated fiber tracts revealed reduced frontal connectivity to the target region.LimitationsThis is an interim report, with limited conclusions.ConclusionThis study of MFB-DBS shows similar rapid anti-depressant effects within the first week of stimulation as initially reported by Schlaepfer et al. (2013). Implementation of anhedonia measurements would greatly augment characterization of the striking motivational effects observed. We urge others to pursue this target to further prove efficacy.ClinicalTrials.gov (identifier: NCT02046330) https://clinicaltrials.gov/ct2/show/NCT02046330