A Decade of Progress in Deep Brain Stimulation of the Subcallosal Cingulate for the Treatment of Depression.

Sharafuddin Khairuddin,Wei Ling Lim,Fung Yin Ngo,Ying-Shing Chan,Man-Lung Fung,Naveed Ahmed Khan,Luca Aquili,Yasin Temel,Lee Wei Lim

doi:10.3390/jcm9103260

Abstract

Major depression contributes significantly to the global disability burden. Since the first clinical study of deep brain stimulation (DBS), over 446 patients with depression have now undergone this neuromodulation therapy, and 29 animal studies have investigated the efficacy of subgenual cingulate DBS for depression. In this review, we aim to provide a comprehensive overview of the progress of DBS of the subcallosal cingulate in humans and the medial prefrontal cortex, its rodent homolog. For preclinical animal studies, we discuss the various antidepressant-like behaviors induced by medial prefrontal cortex DBS and examine the possible mechanisms including neuroplasticity-dependent/independent cellular and molecular changes. Interestingly, the response rate of subcallosal cingulate Deep brain stimulation marks a milestone in the treatment of depression. DBS achieved response and remission rates of 64–76% and 37–63%, respectively, from clinical studies monitoring patients from 6–24 months. Although some studies showed its stimulation efficacy was limited, it still holds great promise as a therapy for patients with treatment-resistant depression. Overall, further research is still needed, including more credible clinical research, preclinical mechanistic studies, precise selection of patients, and customized electrical stimulation paradigms.

Highlights

Major depressive disorder (MDD) contributes significantly to the global disability burden and social burden [1,2]
Suppression of gamma oscillations by deep brain stimulation (DBS) during working memory performance and the treatment efficacy of DBS for Treatment-resistant depression (TRD) may be associated with the improved GABAergic neurotransmission, previously shown to be deficient in MDD.The present study suggests that modifying treatment parameters to achieve suppression of gamma oscillations and increased theta-gamma coupling may lead to optimized DBS efficacy for TRD
In a study from 2003 to 2006 by Lozano et al on chronic DBS in 20 patients with an average of 6.9 years of current major depressive episode (MDE), 11 patients responded, but seven remitted [72], which was similar to the response and remission rates of Mayberg et al In a 3.5-year follow-up study, the response rate was consistent across time points, but the remission rate increased from 18.8% to 42.9% at the last visit [18]

Summary

Introduction

Major depressive disorder (MDD) contributes significantly to the global disability burden and social burden [1,2]. In the US from 2005 to 2010, the economic burden of patients with major depressive disorder increased by 21.5% to $210.5 billion [3]. Pharmacological antidepressants first appeared in the late 20th century and these first-generation drugs became the first line treatment for depression [12]. Treatment-resistant depression (TRD) is the failure to respond to the three different classes of treatment: antidepressants, psychotherapy, or electroconvulsive therapy given at a sufficient dose and time [14,15]. 20% to 30% of patients are refractory to pharmacotherapy and nearly 60% respond inadequately [16,17], which can result in worse clinical responses, leading to additional social burdens [18]. As the pathogenesis of MDD involves multiple structures, a broad-acting safe therapy needs to be developed [19,20]

Objectives

Methods

Findings

Conclusion