A narrative review on invasive brain stimulation for treatment-resistant depression

Abstract

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Conflicts of interest in invasive brain stimulation research

“…We read with great interest the recently published manuscript “A narrative review on invasive brain stimulation for treatment-resistant depression” by Dandekar et al 1 Since major depressive disorder is highly prevalent, associated with significant impairment, and patients who do not respond to therapy face multiple challenges, it is of utmost importance to develop innovative and personalized interventions. The authors reviewed several studies on different treatment modalities, including case reports, cohort studies, open-label, and randomized clinical trials.…”

Concomitant deep brain stimulation and vagus nerve stimulation for treatment-resistant depression: a case report

“… 4 , 5 Among the pharmacological and non-pharmacological interventions for TRD, vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are invasive brain stimulation techniques that have shown positive efficacy and safety results. 6 , 7 Concomitant treatment with both interventions has not yet been reported in the literature. This report presents a case in which DBS and VNS were co-administered in a patient with TRD.…”

“… 8 In addition, VNS has been associated with increased neuroplasticity markers, such as brain-derived neurotrophic factor. 7 In MFB-DBS, the impact on the reward pathway seems to have played a role in the response. Stimulation of the reward pathway in MFB-DBS is associated with activation of dopamine receptors in the prefrontal cortex 9 and increased dopamine D1 and D2 receptor mRNA expression.…”

“…Stimulation of the reward pathway in MFB-DBS is associated with activation of dopamine receptors in the prefrontal cortex 9 and increased dopamine D1 and D2 receptor mRNA expression. 7 Furthermore, higher brain-derived neurotrophic factor levels have been described in MFB-DBS. 7 , 10 …”

“… 7 Furthermore, higher brain-derived neurotrophic factor levels have been described in MFB-DBS. 7 , 10 …”