scholarly journals Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis

BMJ ◽  
2019 ◽  
pp. l1079 ◽  
Author(s):  
Julian Mutz ◽  
Vijeinika Vipulananthan ◽  
Ben Carter ◽  
René Hurlemann ◽  
Cynthia H Y Fu ◽  
...  

AbstractObjectiveTo estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults.DesignSystematic review with pairwise and network meta-analysis.Data sourcesElectronic search of Embase, PubMed/Medline, and PsycINFO up to 8 May 2018, supplemented by manual searches of bibliographies of several reviews (published between 2009 and 2018) and included trials.Eligibility criteria for selecting studiesClinical trials with random allocation to electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive (rTMS), accelerated, priming, deep, and synchronised), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS), or sham therapy.Main outcome measuresPrimary outcomes were response (efficacy) and all cause discontinuation (discontinuation of treatment for any reason) (acceptability), presented as odds ratios with 95% confidence intervals. Remission and continuous depression severity scores after treatment were also examined.Results113 trials (262 treatment arms) that randomised 6750 patients (mean age 47.9 years; 59% women) with major depressive disorder or bipolar depression met the inclusion criteria. The most studied treatment comparisons were high frequency left rTMS and tDCS versus sham therapy, whereas recent treatments remain understudied. The quality of the evidence was typically of low or unclear risk of bias (94 out of 113 trials, 83%) and the precision of summary estimates for treatment effect varied considerably. In network meta-analysis, 10 out of 18 treatment strategies were associated with higher response compared with sham therapy: bitemporal ECT (summary odds ratio 8.91, 95% confidence interval 2.57 to 30.91), high dose right unilateral ECT (7.27, 1.90 to 27.78), priming transcranial magnetic stimulation (6.02, 2.21 to 16.38), magnetic seizure therapy (5.55, 1.06 to 28.99), bilateral rTMS (4.92, 2.93 to 8.25), bilateral theta burst stimulation (4.44, 1.47 to 13.41), low frequency right rTMS (3.65, 2.13 to 6.24), intermittent theta burst stimulation (3.20, 1.45 to 7.08), high frequency left rTMS (3.17, 2.29 to 4.37), and tDCS (2.65, 1.55 to 4.55). Network meta-analytic estimates of active interventions contrasted with another active treatment indicated that bitemporal ECT and high dose right unilateral ECT were associated with increased response. All treatment strategies were at least as acceptable as sham therapy.ConclusionsThese findings provide evidence for the consideration of non-surgical brain stimulation techniques as alternative or add-on treatments for adults with major depressive episodes. These findings also highlight important research priorities in the specialty of brain stimulation, such as the need for further well designed randomised controlled trials comparing novel treatments, and sham controlled trials investigating magnetic seizure therapy.

2018 ◽  
Author(s):  
Julian Mutz ◽  
Vijeinika Vipulananthan ◽  
Ben Carter ◽  
Rene Hurlemann ◽  
Cynthia H Y Fu ◽  
...  

Background: Non-surgical brain stimulation techniques have been applied as tertiary treatments in major depression. However, the relative efficacy and acceptability of individual protocols is uncertain. Our aim was to estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults. Methods: Embase, PubMed/MEDLINE and PsycINFO were searched up until May 8, 2018, supplemented by manual searches of bibliographies of recent reviews and included trials. We included clinical trials with random allocation to electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), accelerated TMS (aTMS), priming TMS (pTMS), deep TMS (dTMS), theta burst stimulation (TBS), synchronised TMS (sTMS), magnetic seizure therapy (MST) or transcranial direct current stimulation (tDCS) protocols or sham. Data were extracted from published reports and outcomes were synthesised using pairwise and network random-effects meta-analysis. Primary outcomes were response (efficacy) and all-cause discontinuation (acceptability). We computed odds ratios (OR) with 95% confidence intervals (CI). Remission and continuous post-treatment depression severity scores were also examined. Results: 113 trials (262 treatment arms) randomising 6,750 patients (mean age = 47.9 years; 59% female) with major depressive disorder or bipolar depression met our inclusion criteria. In terms of efficacy, 10 out of 18 treatment protocols were associated with higher response relative to sham in network meta-analysis: bitemporal ECT (OR=8.91, 95%CI 2.57-30.91), high-dose right-unilateral ECT (OR=7.27, 1.90-27.78), pTMS (OR=6.02, 2.21-16.38), MST (OR=5.55, 1.06-28.99), bilateral rTMS (OR=4.92, 2.93-8.25), bilateral TBS (OR=4.44, 1.47-13.41), low-frequency right rTMS (OR=3.65, 2.13-6.24), intermittent TBS (OR=3.20, 1.45-7.08), high-frequency left rTMS (OR=3.17, 2.29-4.37) and tDCS (OR=2.65, 1.55-4.55). Comparing active treatments, bitemporal ECT and high-dose right-unilateral ECT were associated with increased response. All treatment protocols were at least as acceptable as sham treatment. Conclusion: We found that non-surgical brain stimulation techniques constitute viable alternative or add-on treatments for adult patients with major depressive episodes. Our findings also highlight the need to consider other patient and treatment-related factors in addition to antidepressant efficacy and acceptability when making clinical decisions; and emphasize important research priorities in the field of brain stimulation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeffrey D. Voigt ◽  
Andrew F. Leuchter ◽  
Linda L. Carpenter

AbstractPatients with major depressive disorder (MDD) may be refractory to or have contraindications that preclude treatment with antidepressant pharmacotherapies. Alternative therapies such as repetitive transcranial magnetic stimulation (rTMS) continue to evolve, and include theta burst stimulation (TBS), which has advantages over conventional rTMS. The aim of this study was to identify and meta-analyze efficacy data from all randomized controlled trials (RCTs) investigating TBS as a treatment for MDD. Published reports of RCTs (January 1, 2010 to October 23, 2020) were identified via systematic searches in computerized databases, followed by review of individual reports for inclusion. Inclusion criteria included primary diagnosis of MDD ≥ 1 week duration of therapy with ≥10 sessions, and treatment with any form of TBS. The Cochrane GRADE methodology and PRISMA criteria were used for evaluation of individual trials. Data from ten RCTs were included, representing 667 patients. Of these, 8 RCTs compared TBS to sham treatment and one compared TBS to standard rTMS (i.e., high frequency stimulation over left dorsolateral prefrontal cortex [HFL]). Quality of evidence assessment yielded high confidence in the finding of TBS being superior to sham on response measured by the Hamilton Depression Rating Scale (HRSD) (RR = 2.4; 95% CI: 1.27 to 4.55; P = 0.007; I2 = 40%). Comparison of HRSD response rates for TBS versus rTMS produced no statistically significant difference (RR = 1.02; 95% CI: 0.85 to 1.23; P = 0.80; I2 = 0%). The incidence of adverse events between TBS and rTMS was not statistically different. The findings of a positive effect of TBS vs. sham, and noninferiority of TBS vs. standard HFL rTMS support the continued development of TBS to treat depression.


Author(s):  
Christian Plewnia ◽  
Bettina Brendel ◽  
Tobias Schwippel ◽  
Vanessa Nieratschker ◽  
Thomas Ethofer ◽  
...  

AbstractRepetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) is currently evolving as an effective and safe therapeutic tool in the treatment of major depressive disorder (MDD). However, already established rTMS treatment paradigms are rather time-consuming. With theta burst stimulation (TBS), a patterned form of rTMS, treatment time can be substantially reduced. Pilot studies and a randomized controlled trial (RCT) demonstrate non-inferiority of TBS to 10 Hz rTMS and support a wider use in MDD. Still, data from placebo-controlled multicenter RCTs are lacking. In this placebo-controlled multicenter study, 236 patients with MDD will be randomized to either intermittent TBS (iTBS) to the left and continuous TBS (cTBS) to the right dlPFC or bilateral sham stimulation (1:1 ratio). The treatment will be performed with 80% resting motor threshold intensity over six consecutive weeks (30 sessions). The primary outcome is the treatment response rate (Montgomery-Asberg Depression Rating Scale reduction ≥ 50%). The aim of the study is to confirm the superiority of active bilateral TBS compared to placebo treatment. In two satellite studies, we intend to identify possible MRI-based and (epi-)genetic predictors of responsiveness to TBS therapy. Positive results will support the clinical use of bilateral TBS as an advantageous, efficient, and well-tolerated treatment and pave the way for further individualization of MDD therapy.Trial registration: ClinicalTrials.gov (NCT04392947).


2014 ◽  
Vol 205 (4) ◽  
pp. 268-274 ◽  
Author(s):  
Pim Cuijpers ◽  
Sander L. Koole ◽  
Annemiek van Dijke ◽  
Miquel Roca ◽  
Juan Li ◽  
...  

BackgroundThere is controversy about whether psychotherapies are effective in the treatment of subclinical depression, defined by clinically relevant depressive symptoms in the absence of a major depressive disorder.AimsTo examine whether psychotherapies are effective in reducing depressive symptoms, reduce the risk of developing major depressive disorder and have comparable effects to psychological treatment of major depression.MethodWe conducted a meta-analysis of 18 studies comparing a psychological treatment of subclinical depression with a control group.ResultsThe target groups, therapies and characteristics of the included studies differed considerably from each other, and the quality of many studies was not optimal. Psychotherapies did have a small to moderate effect on depressive symptoms against care as usual at the post-test assessment (g = 0.35, 95% CI 0.23–0.47; NNT = 5, 95% CI 4–8) and significantly reduced the incidence of major depressive episodes at 6 months (RR = 0.61) and possibly at 12 months (RR = 0.74). The effects were significantly smaller than those of psychotherapy for major depressive disorder and could be accounted for by non-specific effects of treatment.ConclusionsPsychotherapy may be effective in the treatment of subclinical depression and reduce the incidence of major depression, but more high-quality research is needed.


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