Introduction: Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to be effective in rapidly improving treatment resistant depression (TRD). This report is an update to our recently published results (Fenoy et al., 2016).

Methods: In this analysis of an ongoing study, we assessed the efficacy of MFB-DBS in a cohort of eight TRD patients over a 52-week period using improvement on the Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary outcome measure. Implanted patients entered a 4-week single-blinded sham stimulation period prior to stimulation initiation.

Results: Upon stimulation at target intraoperatively, responders reported immediate increases in energy and motivation. There was a significant mean change in mood during the 4 week sham stimulation phase (34% mean MADRS reduction, p = 0.03), but no significant difference upon stimulation initiation at 1 week relative to end sham. However, the difference in MADRS score between baseline and 2 weeks of active stimulation was significant (mean change = 17 pts, 49% reduction, p < 0.001). One patient withdrew from study participation. At 26 weeks, 5 of 6 remaining patients have >50% improvement of MADRS (mean improvement = 27 pts, 77% reduction, p = 0.002). At 52 weeks, 4 of remaining 5 patients continue to have >70% decrease in MADRS scores relative to baseline. 2 patients are currently active in the study and have not completed all assessments. One patient failed to respond. Evaluation of modulated fiber tracts reveals significant common frontal connectivity to the target region in all responders.

Conclusions: This study of MFB-DBS confirms rapid anti-depressant effects are observed with stimulation, as reported by Schlaepfer et al. (2013). Although the insertional response itself is significant, the effect becomes more pronounced with time after stimulation onset.

Patient Care: By identifying an effective treatment intervention that can reproducibly cause remission in patients who otherwise have no treatment options in resistant depression, millions of patients worldwide can get help.

Learning Objectives: By the conclusion of this session, participants should be able to 1. Describe the pervasiveness of treatment resistant depression in society with lack of available approved treatments. 2. Identify how interventions such as deep brain stimulation can impact/improve psychiatric diseases through modulation at specific nodes within fiber tract-defined circuits . 3. Recognize the utility of deep brain stimulation in causing remission from treatment resistant depression. 4. Discuss how the use of diffusion tensor imaging can elucidate fiber tracts that can be modulated, which are thought to be key to the incurred anti-depressant effect.

References: 1. Fenoy AJ, Schulz P, Selvaraj S, Burrows C, Spiker D, Cao B, et al. Deep brain stimulation of the medial forebrain bundle: distinctive responses in resistant depression. J Affect Disord 2016; 203:143-151. 2. Schlaepfer TE, Bewernick BH, Kayser S, Madler B, Coenen VA. Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry 2013; 73:1204-12.