scholarly journals Placebo response in treatment resistant depression: a systematic review and meta-analysis of multiple treatment modalities

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S261-S262
Author(s):  
Brett D M Jones ◽  
Cory R. Weissman ◽  
Jewel Karbi ◽  
Tya Vine ◽  
Louise S. Mulsant ◽  
...  
Keyword(s):  
Systematic Review ◽  
Brain Stimulation ◽  
Placebo Effect ◽  
Meta Analysis ◽  
Specific Treatment ◽  
Placebo Response ◽  
Treatment Modalities ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

AimsThe placebo response in depression clinical trials is a major contributing factor for failure to establish the efficacy of novel and repurposed treatments. However, it is not clear as to what the placebo response in treatment-resistant depression (TRD) patients is or whether it differs across treatment modalities. Our objective was to conduct a systematic review and meta-analysis of the magnitude of the placebo response in TRD patients across different treatment modalities and its possible moderators.MethodSearches were conducted on MEDLINE and PsychInfo from inception to January 24, 2020. Only studies that recruited TRD patients and randomization to a placebo (or sham) arm in a pharmacotherapy, brain stimulation, or psychotherapy study were included (PROSPERO 2020 CRD42020190465). The primary outcome was the Hedges’ g for the reported depression scale using a random-effects model. Secondary outcomes included moderators assessed via meta-regression and response and remission rate. Heterogeneity was evaluated using the Egger's Test and a funnel plot. Cochrane Risk of Bias Tool was used to estimate risks.Result46 studies met our inclusion criteria involving a total of 3083 participants (mean (SD) age: 45.7 (6.2); female: 52.4%). The pooled placebo effect for all modalities was large (N = 3083, g = 1.08 ,95% CI [0.95-1.20)I 2 = 0.1). The placebo effect in studies of specific treatment modalities did not significantly differ: oral medications g = 1.14 (95%CI:0.99-1.29); parenteral medications g = 1.32 (95%CI:0.59-2.04); ayahuasca g = 0.47 (95%CI:-0.28-1.17); rTMS g = 0.93 (95%CI:0.63-1.23); tDCS g = 1.32 (95%CI:0.52-2.11); invasive brain stimulation g = 1.06 (95%CI:0.64-1.47). There were no psychotherapy trials that met our eligibility criteria. Similarly, response and remission rates were comparable across modalities. Heterogeneity was large. Two variables predicted a lager placebo effect: open-label prospective design (B:0.32, 95%CI: 0.05-0.58; p:0.02) and sponsoring by a pharmaceutical or medical device company (B:0.39, 95%CI:0.13-0.65, p:0.004)). No risk of publication bias was found.ConclusionThe overall placebo effect in TRD studies was large (g = 1.08) and did not differ among treatment modalities. A better understanding of the placebo response in TRD will require: standardizing the definition of TRD, head-to-head comparisons of treatment modalities, an assessment of patient expectations and experiences, and standardized reporting of outcomes.

scholarly journals Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis

2018 ◽  
Vol 214 (1) ◽  
pp. 42-51 ◽  
Author(s):  
Rebecca Strawbridge ◽  
Ben Carter ◽  
Lindsey Marwood ◽  
Borwin Bandelow ◽  
Dimosthenis Tsapekos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Psychological Control ◽  
Meta Analysis ◽  
Treatment Modalities ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
The Past ◽  
Grant Support ◽  
Resistant Depression ◽  
Research Grant

BackgroundDepression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD.MethodParticipants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions.ResultsOf 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25–1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23–1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81–1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.08–1.30) and psychological (ES = 1.43, 95% CI 0.50–2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66–0.91) and psychological control (ES = 0.94, 95% CI 0.36–1.52).ConclusionsDespite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.Declaration of interestIn the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.

scholarly journals Protocol for a systematic review and meta-analysis of the placebo response in treatment-resistant depression: comparison of multiple treatment modalities

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e041349
Author(s):  
Brett D M Jones ◽  
Cory R Weissman ◽  
Lais B Razza ◽  
M Ishrat Husain ◽  
Andre R Brunoni ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Placebo Response ◽  
Treatment Modalities ◽  
Randomised Control Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Academic Journal ◽  
Multiple Treatment ◽  
Resistant Depression ◽  
Meta Analyses

IntroductionThe high placebo response in depression treatment trials is a major contributing factor for randomised control trial failure to establish efficacy of novel or repurposed treatments in treatment-resistant depression (TRD) and major depressive disorder in general. Though there have been a number of meta-analyses and primary research studies evaluating the placebo response in non-TRD, placebo response in TRD is poorly understood. It is important to understand the placebo response of TRD as treatments are only moderately effective and up to 1/3 of patients will experience TRD.Methods and analysisWe will conduct a search of electronic databases (MEDLINE and PsychINFO) from inception to 24th January 2020 including randomised, placebo-controlled trials of pharmacological, somatic and psychological interventions for adults with TRD. TRD will be defined as a failure to respond to at least two interventions of adequate dose or duration. We will also search reference lists from review articles. We will perform several meta-analyses to quantify the placebo response for each treatment modality. Regression analysis will explore potential contributing demographic and clinical variables to the placebo response. We will use Cochrane risk of bias tool.Ethics and disseminationThere is no research ethics board approval required. The dissemination plan is to publish results in a peer-reviewed academic journal.PROSPERO registration number190 465.

scholarly journals Efficacy and acceptability of adjunctive psychological and pharmacological interventions for treatment-resistant depression: protocol for a systematic review and network meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e028538 ◽  
Author(s):  
Muhammad Ishrat Husain ◽  
Rebecca Strawbridge ◽  
Ben Carter ◽  
Brett D M Jones ◽  
Allan Young ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Treatment Options ◽  
Treatment Modalities ◽  
Evidence Based ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Academic Journal ◽  
Resistant Depression ◽  
Randomised Controlled

IntroductionMajor depressive disorder (MDD) is a common debilitating illness worldwide. The vast majority of patients with MDD will not achieve remission with first-line treatment and despite the availability of different treatment modalities, at least one-third of patients experience treatment-resistant depression (TRD). There continues to be a paucity of research focused on treatment options for patients with TRD thus treatment decisions are largely based on patient and clinician preference as opposed to evidence-based practice. Herein we propose a systematic review and network meta-analysis (NMA) of available pharmacological and psychological augmentation treatments for TRD, to inform evidence-based management of TRD.Methods and analysisWe plan to conduct a search of electronic databases (MEDLINE and ISIWEB) of all dates from inception for randomised controlled trials of pharmacological and psychological augmentation interventions for adults with TRD. Articles for review will be included based upon consensus from two authors. Pharmaceutical companies will be contacted for access to any unpublished data. An NMA will compare the effectiveness pharmacological adjunctive agents for TRD using preanalysis/postanalysis, assuming consistency and transitivity.Ethics and disseminationThis project does not require research ethics board approval. The dissemination plan is to present findings at international scientific meetings and publishing results in a peer-reviewed academic journal.PROSPERO registration numberCRD42019132588.

scholarly journals Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis – CORRIGENDUM

2018 ◽  
Vol 214 (5) ◽  
pp. 308-308
Author(s):  
Rebecca Strawbridge ◽  
Ben Carter ◽  
Lindsey Marwood ◽  
Borwin Bandelow ◽  
Dimosthenis Tsapekos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

scholarly journals Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes

2014 ◽  
Vol 11 (3) ◽  
pp. 475-484 ◽  
Author(s):  
Takashi Morishita ◽  
Sarah M. Fayad ◽  
Masa-aki Higuchi ◽  
Kelsey A. Nestor ◽  
Kelly D. Foote
Keyword(s):  
Systematic Review ◽  
Deep Brain Stimulation ◽  
Clinical Outcomes ◽  
Brain Stimulation ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Deep Brain

Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis

2020 ◽  
Vol 32 (5-6) ◽  
pp. 477-490 ◽  
Author(s):  
Ben Carter ◽  
Rebecca Strawbridge ◽  
Muhammad Ishrat Husain ◽  
Brett D. M. Jones ◽  
Roxanna Short ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Relative Effectiveness ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

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

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.

scholarly journals Augmentation therapies for treatment-resistant depression: a systematic review and meta-analysis

2019 ◽  
Vol 254 ◽  
pp. 153
Author(s):  
Dr Rebecca Strawbridge ◽  
Dr Ben Carter ◽  
Dr Lindsey Marwood ◽  
Professor Borwin Bandelow ◽  
Dimosthenis Tsapekos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression
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