An Integrated Analysis of Olanzapine/Fluoxetine Combination in Clinical Trials of Treatment-Resistant Depression

Compared with other inhaled anaesthetics, sevoflurane has a faster onset and offset, causes less irritation to the mucous membranes, and has a better safety profile. These characteristics warrant investigating the effect of sevoflurane in depression. In this Case Report, we describe that sevoflurane treatment was feasible and well tolerated by a patient with treatment-resistant depression (TRD). Sevoflurane had rapid and durable antidepressant effects, with few adverse effects. Moreover, the patient showed significant improvements in neurocognitive measurements. Our preliminary results suggest that further clinical trials are needed to determine the independent efficacy and safety of sevoflurane in patients with TRD.

Download Full-text

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Molecular Psychiatry ◽

10.1038/s41380-021-01381-x ◽

2021 ◽

Author(s):

Luca Sforzini ◽

Courtney Worrell ◽

Melisa Kose ◽

Ian M. Anderson ◽

Bruno Aouizerate ◽

...

Keyword(s):

Clinical Trials ◽

Lived Experience ◽

Delphi Method ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Regulatory Bodies ◽

Resistant Depression ◽

Operational Criteria ◽

Definition Of ◽

International Experts

AbstractCriteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Download Full-text

“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.

Download Full-text

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

Frontiers in Neuroscience ◽

10.3389/fnins.2021.655412 ◽

2021 ◽

Vol 15 ◽

Author(s):

Youliang Wu ◽

Jiajie Mo ◽

Lisen Sui ◽

Jianguo Zhang ◽

Wenhan Hu ◽

...

Keyword(s):

Clinical Trials ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Meta Analysis ◽

Cochrane Library ◽

Efficacy And Safety ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Resistant Depression ◽

Deep Brain

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.

Download Full-text