A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression

Dougherty, Darin D.; Rezai, Ali R.; Carpenter, Linda L.; Howland, Robert H; Bhati, Mahendra T.; O’Reardon, John P.; Eskandar, Emad N.; Baltuch, Gordon H.; Machado, André De Sousa; Kondziolka, Douglas; Cusin, Cristina; Evans, Karleyton C.; Price, Lawrence H.; Jacobs, Karen; Pandya, Mayur; Denko, Timothey; Tyrka, Audrey R.; Brelje, Tim; Deckersbach, Thilo; Kubu, Cynthia S.; Malone, Donald A.

doi:10.1016/j.biopsych.2014.11.023

Cited by 428 publications

(321 citation statements)

References 17 publications

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“…179 However, a larger, sham-controlled study of VC/VS stimulation did not show the same degree of positive results. 57 Thirty patients with TRD were recruited in a multisite trial that started with a 16-week period of either sham or active stimulation. Of those receiving active stimulation, 3 of 15 had a clinical response, but 2 of 15 had a clinical response from sham stimulation.…”

Section: 211mentioning

confidence: 99%

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“…57,89,179,211 Suicidality is also a major concern, with more than 10% of patients reported as attempting suicide in a larger study. 57 Stimulationrelated adverse effects are seen most often with the ventral contacts closest to the VS, which are often the most efficacious for treatment as well. 179 Physiological effects of stimulation include tachycardia, nausea, changes in respiratory rate, and sweating; behavioral or psychological adverse effects include mania, hypomania, anxiety, panic, fear, worsening depression, unpleasant tastes or smells, and facial motor tics.…”

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confidence: 99%

“…89,179,215 In neuropsychological testing, 1 study reported a statistically significant but clinically questionable decline in some areas of cognitive performance, whereas other trials have noted an improvement in recall. 57,89,179 …”

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Deep brain stimulation for psychiatric disorders: where we are now

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Raslan

et al. 2015

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Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

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Deep brain stimulation for psychiatric disorders: where we are now

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“…Thus, VStargeted DBS also seems to influence functional connections between VS and mediofrontal regions, though ECT and DBS clearly involve different modes of neurostimulation and central nervous system access. In contrast to ECT, however, VS-targeted DBS may be less universally effective in improving symptoms of depression as demonstrated in a recent randomized trial (Dougherty et al 2015). Future neuroimaging research comparing how the same brain networks (e.g., fronto-striatal) are affected by different neurostimulation therapies may help define the functional circuitry most optimal for stimulation targeting, which could be an important means of improving therapies (Fox et al 2014).…”

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confidence: 99%

Desynchronization and Plasticity of Striato-frontal Connectivity in Major Depressive Disorder

et al. 2015

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Major depressive disorder (MDD) is associated with dysfunctional corticolimbic networks, making functional connectivity studies integral for understanding the mechanisms underlying MDD pathophysiology and treatment. Resting-state functional connectivity (RSFC) studies analyze patterns of temporally coherent intrinsic brain activity in "resting-state networks" (RSNs). The default-mode network (DMN) has been of particular interest to depression research; however, a single RSN is unlikely to capture MDD pathophysiology in its entirety, and the DMN itself can be characterized by multiple RSNs. This, coupled with conflicting previous results, underscores the need for further research. Here, we measured RSFC in MDD by targeting RSNs overlapping with corticolimbic regions and further determined whether altered patterns of RSFC were restored with electroconvulsive therapy (ECT). MDD patients exhibited hyperconnectivity between ventral striatum (VS) and the ventral default-mode network (vDMN), while simultaneously demonstrating hypoconnectivity with the anterior DMN (aDMN). ECT influenced this pattern: VS-vDMN hyperconnectivity was significantly reduced while VS-aDMN hypoconnectivity only modestly improved. RSFC between the salience RSN and dorsomedial prefrontal cortex was also reduced in MDD, but was not affected by ECT. Taken together, our results support a model of ventral/dorsal imbalance in MDD and further suggest that the VS is a key structure contributing to this desynchronization.

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Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults

et al. 2021

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IMPORTANCEThe placebo effect in depression clinical trials is a substantial factor associated with failure to establish efficacy of novel and repurposed treatments. However, the magnitude of the placebo effect and whether it differs across treatment modalities in treatment-resistant depression (TRD) is unclear.OBJECTIVE To examine the magnitude of the placebo effect in patients with TRD across different treatment modalities and its possible moderators. DATA SOURCESSearches were conducted on MEDLINE, Web of Science, and PsychInfo from inception to June 21, 2021. STUDY SELECTION Randomized clinical trials (RCTs) were included if they recruited patients with TRD and randomized them to a placebo or sham arm and a pharmacotherapy, brain stimulation, or psychotherapy arm. DATA EXTRACTION AND SYNTHESIS Independent reviewers used standard forms for data extraction and quality assessment. Random-effects analyses and standard pairwise meta-analyses were performed. MAIN OUTCOMES AND MEASURES The primary outcome was the Hedges g value for the reported depression scales. Secondary outcomes included moderators assessed via meta-regression and response and remission rates. Heterogeneity was assessed with the I 2 test, and publication bias was evaluated using the Egger test and a funnel plot. Cochrane Risk of Bias Tool was used to estimate risks. RESULTS Fifty RCTs were included involving various types of placebo or sham interventions with a total of 3228 participants (mean [SD] age, 45.8 [6.0] years; 1769 [54.8%] female). The pooledplacebo effect size for all modalities was large (g = 1.05; 95% CI, 0.91-1.1); the placebo effect size in RCTs of specific treatment modalities did not significantly differ. Similarly, response and remission rates associated with placebo were comparable across modalities. Heterogeneity was large. Three variables were associated with a larger placebo effect size: open-label prospective treatment before double-blind placebo randomization (β = 0.35; 95% CI, 0.11 to 0.59; P = .004), later year of publication (β = 0.03; 95% CI, 0.003 to 0.05; P = .03), and industry-sponsored trials (β = 0.34; 95% CI, 0.09 to 0.58; P = .007). The number of failed interventions was associated with the probability a smaller placebo effect size (β = −0.12; 95% CI, −0.23 to −0.01, P = .03). The Egger test result was not significant for small studies' effects. (continued) Key Points Question What is the placebo effect magnitude in different treatment modalities used for management of patients with treatment-resistant depression? Findings In this systematic review and meta-analysis of 3228 patients with treatment-resistant depression in 50 randomized clinical trials, the placebo effect size was large and consistent across treatment modalities. Response and remission rates associated with placebo effect were comparable across modalities.Meaning The findings of this study suggest a placebo effect size benchmark may be used to interpret the findings of past and future clinical trials.

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A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression

Cited by 428 publications

References 17 publications

Deep brain stimulation for psychiatric disorders: where we are now

Deep brain stimulation for psychiatric disorders: where we are now

Desynchronization and Plasticity of Striato-frontal Connectivity in Major Depressive Disorder

Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults

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