Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up

S Raymaekers,L Gabriëls,C Bervoets,B Nuttin,L Luyten

doi:10.1038/tp.2017.66

Abstract

We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients. The 17-item Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. During the first crossover, patients received IC/BST stimulation versus no stimulation in random order (2 × 1 weeks). During the second crossover (3 × 2 months), patients received IC/BST versus ITP versus no stimulation. Patients and evaluators were blinded for stimulation conditions. All patients (n=7) were followed up for at least 3 years (3–8 years) after implantation. Six patients completed the first crossover and five patients completed the second. During the first crossover, mean (s.d.) HAM-D scores were 21.5 (2.7) for no stimulation and 11.5 (8.8) for IC/BST stimulation. During the second crossover, HAM-D scores were 15.4 (7.5) for no stimulation, 7.6 (3.8) for IC/BST stimulation and 11.2 (7.5) for ITP stimulation. The final sample size was too small to statistically analyze this second crossover. At last follow-up, only one patient preferred ITP over IC/BST stimulation. Two patients, with a history of suicide attempts before implantation, committed suicide during the follow-up phases of this study. Our data indicate that, in the long term, both ITP and IC/BST stimulation may alleviate depressive symptoms in patients suffering from TRD.

Highlights

Major depressive disorder (MDD) is defined as the presence of depressed mood or anhedonia for more than 2 weeks, accompanied by additional symptoms
Functional imaging studies have resulted in a better understanding of the brain regions involved in the pathology of MDD.[11]
We further explored the inferior thalamic peduncle (ITP) as a deep brain stimulation (DBS) target

Summary

Introduction

Major depressive disorder (MDD) is defined as the presence of depressed mood or anhedonia for more than 2 weeks, accompanied by additional symptoms (for example, suicidal thoughts, sleep disturbances and so on). MDD is a burdensome disorder with a substantial and increasing impact on society,[1,2] and a lifetime prevalence of up to 17%,3 with recent findings suggesting an even higher prevalence.[4] Treatment strategies include pharmacotherapy,[5] psychotherapy,[6] repetitive transcranial magnetic stimulation (rTMS)[7] and electroconvulsive therapy (ECT).[8] Up to 30% of patients with MDD do not adequately respond to treatment. In these treatment-resistant MDD (TRD) patients, the disorder often takes a chronic, disabling course.[9,10].

Objectives

Methods

Results