Deep Brain Stimulation in Treatment-Resistant Depression: A Systematic Review and Meta-Analysis on Efficacy and Safety

Objective: Deep brain stimulation (DBS) has shown promising outcomes as new therapeutic opportunities for patients with treatment-resistant depression (TRD) who do not respond adequately to several consecutive treatments. This study aims to systematically review and conduct a meta-analysis on the efficacy and safety of DBS for TRD.Method: The literature was comprehensively reviewed using Medline, Google scholar, Cochrane library, Embase, and World Health Organization International Clinical Trials Registry Platform until January 2019. The studied outcomes included response, remission, recurrence, and adverse events (AEs) rates, and were reported as the rate ratio (RR) or pooled estimate with a 95% confidence interval (95% CI). Heterogeneity was measured by an I-square test and a sensitive analysis.Results: A total of 17 studies involving 7 DBS targets were included. For efficacy, DBS treatment was statistically beneficial for TRD, and the response, remission, and recurrence rates were 56% (ranging from 43 to 69%), 35% (ranging from 27 to 44%), and 14% (ranging from 4 to 25%), respectively. However, only two randomized-controlled trials (RCTs) considered the invalidity of DBS (RR = 1.45, 95% CI = 0.50–4.21). For safety, the AEs rate was 67% (ranging from 54 to 80%). The AEs were common and moderate, but the problems related to suicide and suicidal ideation should not be underestimated.Conclusion: These findings suggest that DBS for TRD is considered promising, which should be confirmed by well-designed and large sample studies. Future basic research and comprehensive clinical trials are needed to reach better understanding on the mechanisms of action and optimal targeted structure.

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Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression

Journal of Clinical Medicine ◽

10.3390/jcm9092796 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2796

Author(s):

Frederick L. Hitti ◽

Andrew I. Yang ◽

Mario A. Cristancho ◽

Gordon H. Baltuch

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Meta Analysis ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Significant Difference ◽

Resistant Depression ◽

Meta Regression ◽

K 12 ◽

Deep Brain

Major depressive disorder (MDD) is a leading cause of disability and a significant cause of mortality worldwide. Approximately 30–40% of patients fail to achieve clinical remission with available pharmacological treatments, a clinical course termed treatment-resistant depression (TRD). Numerous studies have investigated deep brain stimulation (DBS) as a therapy for TRD. We performed a meta-analysis to determine efficacy and a meta-regression to compare stimulation targets. We identified and screened 1397 studies. We included 125 citations in the qualitative review and considered 26 for quantitative analysis. Only blinded studies that compared active DBS to sham stimulation (k = 12) were included in the meta-analysis. The random-effects model supported the efficacy of DBS for TRD (standardized mean difference = −0.75, <0 favors active stimulation; p = 0.0001). The meta-regression did not demonstrate a statistically significant difference between stimulation targets (p = 0.45). While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this meta-analysis reveals a significant effect of DBS for the treatment of TRD. Additionally, the majority of trials have demonstrated the safety and efficacy of DBS for this indication. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including electrode placement technique, patient selection, and long-term follow-up is essential for future trial design.

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Exploratory meta-analysis on deep brain stimulation in treatment-resistant depression

Acta Neuropsychiatrica ◽

10.1017/neu.2014.22 ◽

2013 ◽

Vol 26 (6) ◽

pp. 382-384 ◽

Cited By ~ 6

Author(s):

Donald F. Smith

Keyword(s):

Electrical Stimulation ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Meta Analysis ◽

Term Treatment ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Long Term Treatment ◽

Resistant Depression ◽

Deep Brain

ObjectiveDeep brain stimulation is currently an experimental treatment for major depressive disorder. Information is lacking, however, on how sham responding may affect efficacy. This article applies exploratory meta-analysis to address that topic.MethodsData on benefits of deep brain electrical stimulation come from a recent review. Stimulated brain regions included subgenual cingulate, capsular interna, nucleus accumbens, and medial forebrain bundle. Expert opinion plus random number software was used to generate hypothetical values for sham responding.ResultsAn effect size of 1.71 (95% CI: 1.47–1.96) was obtained for deep brain stimulation versus sham treatment in patients suffering from long-term treatment-resistant depression.ConclusionPreliminary findings on deep brain electrical stimulation suggest that the procedure may be 71% more effective than sham treatment. Expressing these findings as patients-needed-to-treat, deep brain electrical stimulation is required by 2.9 patients with long-term treatment-resistant depression in order for one of them to benefit.

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“Nothing to Lose, Absolutely Everything to Gain”: Patient and Caregiver Expectations and Subjective Outcomes of Deep Brain Stimulation for Treatment-Resistant Depression

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.755276 ◽

2021 ◽

Vol 15 ◽

Author(s):

Cassandra J. Thomson ◽

Rebecca A. Segrave ◽

Paul B. Fitzgerald ◽

Karyn E. Richardson ◽

Eric Racine ◽

...

Keyword(s):

Clinical Trials ◽

Deep Brain Stimulation ◽

Informed Consent ◽

Brain Stimulation ◽

Family Needs ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Structured Interviews ◽

Resistant Depression ◽

Deep Brain

Background: How “success” is defined in clinical trials of deep brain stimulation (DBS) for refractory psychiatric conditions has come into question. Standard quantitative psychopathology measures are unable to capture all changes experienced by patients and may not reflect subjective beliefs about the benefit derived. The decision to undergo DBS for treatment-resistant depression (TRD) is often made in the context of high desperation and hopelessness that can challenge the informed consent process. Partners and family can observe important changes in DBS patients and play a key role in the recovery process. Their perspectives, however, have not been investigated in research to-date. The aim of this study was to qualitatively examine patient and caregivers’ understanding of DBS for TRD, their expectations of life with DBS, and how these compare with actual experiences and outcomes.Methods: A prospective qualitative design was adopted. Semi-structured interviews were conducted with participants (six patients, five caregivers) before DBS-implantation and 9-months after stimulation initiation. All patients were enrolled in a clinical trial of DBS of the bed nucleus of the stria terminalis. Interviews were thematically analyzed with data saturation achieved at both timepoints.Results: Two primary themes identified were: (1) anticipated vs. actual outcomes, and (2) trial decision-making and knowledge. The decision to undergo DBS was driven by the intolerability of life with severe depression coupled with the exhaustion of all available treatment options. Participants had greater awareness of surgical risks compared with stimulation-related risks. With DBS, patients described cognitive, emotional, behavioral and physical experiences associated with the stimulation, some of which were unexpected. Participants felt life with DBS was like “a roller coaster ride”—with positive, yet unsustained, mood states experienced. Many were surprised by the lengthy process of establishing optimum stimulation settings and felt the intervention was still a “work in progress.”Conclusion: These findings support existing recommendations for iterative informed consent procedures in clinical trials involving long-term implantation of neurotechnology. These rich and descriptive findings hold value for researchers, clinicians, and individuals and families considering DBS. Narrative accounts capture patient and family needs and should routinely be collected to guide patient-centered approaches to DBS interventions.

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