Deep brain stimulation provides sustained relief for severe depression

Summary: Deep brain stimulation provides a significant reduction in the symptoms of depression for a number of patients with a treatment-resistant form of the disorder.

Source: University of Freiburg

Patients suffering from severe, treatment-resistant depression can benefit both acutely and in the long-term from deep brain stimulation, as researchers from the Medical Center – University of Freiburg and their colleagues from the University Hospital Bonn demonstrate in a current study. The team used thin electrodes to stimulate a deep-seated part of the reward system in the brains of 16 patients. This led to a significant reduction of depression severity in all patients by half, on average. For eight participants, it was reduced below the level regarded as the threshold for a depression requiring treatment. Most of the patients experienced positive stimulation effects within the first week, and they lasted throughout the course of the one-year study. The study was published online in the Nature journal Neuropsychopharmacology on Thursday, 14 March 2019.

“The most compelling outcome from the study is the sustained efficacy in very severely ill patients. Most treatments in psychiatry cease to be efficacious after months and years, we demonstrated for the first time in demonstrating in a relatively large-scale study that deep brain stimulation is a real option for those patients suffering from treatment-resistant, severe depression,” says group leader Prof. Dr. Thomas Schläpfer, head of the Division of Interventional Biological Psychiatry at the Medical Center – University of Freiburg.

Success after Dozens of Unsuccessful Treatments

An estimated 10 to 30 percent of all people with recurring depression do not respond to approved treatments. Deep brain stimulation could be a treatment option for some of these patients. The 16 participants in the FORSEE-II study had suffered from severe depression for 8 to 22 years and had previously undergone an average of 18 drug therapies, 20 electroconvulsive therapies, and 70 hours of psychotherapy. All without success.

Prof. Dr. Volker A. Coenen, first author of the study and director of the Stereotactic and Functional Neurosurgery Unit at the Department of Neurosurgery of the Medical Center – University of Freiburg, and his team implanted the deep brain stimulation systems in the patients medial forebrain bundle of the brain and used them to stimulate the medial forebrain bundle. This brain region is involved in the perception and regulation of pleasure and reward. The area is also significant for motivation and perceived quality of life.

Clear Relief Often within Days

The doctors evaluated the success of the therapy monthly with the help of the established Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS scores of ten study participants already decreased significantly within the first week and remained at a low level. All study participants reacted to the stimulation during the course of the study. Eight of the 16 patients had a MADRS score of under 10 points at the end of the study and thus were regarded as non-depressive. “Our patients had struggled with severe depression for years with no signs of improvement. Deep brain stimulation brought most of them significant relief within days, which lasted throughout the course of the therapy. Other forms of treatment like medication and psychotherapy often lose their effectiveness over the course of time. Absolutely sensational about the study data is that the effect seems to be long-lasting, with the positive effects continuing for years”, says Prof. Schläpfer.

image is a diagram of the dbs implants in the brain
The researchers implanted the deep brain stimulation systems in the patients’ medial forebrain bundle (blue) of the brain, a part of the brain’s reward system. The image is credited to University of Freiburg – Medical Center.

“We know from a pilot study that the stimulation of this brain region is very promising and we are delighted about the replication of these significant effects,” says Prof. Coenen.

Hopes for European Approval of the Method

On the basis of the results, the Freiburg researchers have already begun work on their third study (FORESEE-III). It will involve the treatment of 50 severely depressed patients. Fifteen patients have already been operated upon. “If the follow-up study is as successful as the current one, we have high hopes for receiving European approval of the method,” says Prof. Schläpfer.

About this neuroscience research article

University of Freiburg
Media Contacts:
Thomas Schläpfer – University of Freiburg
Image Source:
The image is credited to University of Freiburg – Medical Center

Original Research: Closed access
“Superolateral medial forebrain bundle deep brain stimulation in major depression: a gateway trial”
Volker A. Coenen, Bettina H. Bewernick, Sarah Kayser, Hannah Kilian, Jan Boström, Susanne Greschus, René Hurlemann, Margaretha Eva Klein, Susanne Spanier, Bastian Sajonz, Horst Urbach & Thomas E. Schlaepfer
Neuropsychopharmacology (2019) doi:10.1038/s41386-019-0369-9


Superolateral Medial Forebrain Bundle Deep Brain Stimulation in Major Depression – A Gateway Trial

Short- and long-term antidepressant effects of deep brain stimulation (DBS) in treatment-resistant depression (TRD) have been demonstrated for several brain targets in open-label studies. For two stimulation targets, pivotal randomized trials have been conducted; both failed a futility analysis. We assessed efficacy and safety of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB) in a small Phase I clinical study with a randomized-controlled onset of stimulation in order to obtain data for the planning of a large RCT. Sixteen patients suffering from TRD received DBS of the slMFB and were randomized to sham or real stimulation for the duration of 2 months after stimulation onset. The primary outcome measure was mean reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) during 12 months of DBS (timeline analysis). Secondary outcomes were the difference in several clinical measures between sham and real stimulation at 8 weeks and during stimulation phases. MADRS ratings decreased significantly from 29.6 (SD 4) at baseline to 12.9 (SD 9) during 12 months of DBS (mean MADRS, n = 16). All patients reached the response criterion, most patients (n = 10) responded within a week; 50% of patients were classified as remitters after 1 year of stimulation. The most frequent side effect was transient strabismus. Both groups (active/sham) demonstrated an antidepressant micro-lesioning effect but patients had an additional antidepressant effect after initiation of stimulation. Both rapid onset and stability of the antidepressant effects of slMFB-DBS were demonstrated as in our previous pilot study. Given recent experiences from pivotal trials in DBS for MDD, we believe that slow, careful, and adaptive study development is germane. After our exploratory study and a large-scale study, we conducted this gateway trial in order to better inform planning of the latter. Important aspects for the planning of RCTs in the field of DBS for severe and chronic diseases are discussed including meaningful phases of intra-individual and between-group comparisons and timeline instead of single endpoint analyses.

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