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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.

ABSTRACT: OBJECTIVE:To estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults. DESIGN:Systematic review with pairwise and network meta-analysis. DATA SOURCES:Electronic 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 STUDIES:Clinical 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 MEASURES:Primary 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. RESULTS:113 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. CONCLUSIONS:These 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.

SUBMITTER: Mutz J

PROVIDER: S-EPMC6435996 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: With the growing importance of research about the association between neuroinflammation and major depressive disorder (MDD), anti-inflammatory agents have been used as a new antidepressant therapy in clinical practice. We conducted a network meta-analysis (NMA) with up-to-date evidence to compare different anti-inflammatory agents for improving the treatment of MDD patients. Methods: To identify eligible randomized clinical trials, four databases (i.e, the Cochrane Library, Web of Science, PubMed and Embase) were searched from inception date to May 31, 2020. Anti-inflammatory agents were defined as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, cytokine inhibitors, statins, pioglitazone, minocycline, N-acetylcysteine (NAC) and omega-3 fatty acid (Omega-3 FA). The main outcomes of this NMA were efficacy, acceptability and remission rate. Risk ratio (RR) was adopted for dichotomous outcomes, and the confidence interval (CI) was set at 95%. STATA 14.0 and R 3.6.3 were used to conduct the NMA. The study protocol was registered with PROSPERO (CRD42020182531). Results: A total of 39 studies, involving 2871 participants, were included in quantitative data synthesis. For efficacy, NSAIDs (RR=0.50, 95%CI: 0.26-0.73) and pioglitazone (RR=0.45, 95%CI: 0.20-0.84) were more favorable than placebo. With respect to acceptability, NSAIDs were more acceptable than placebo (RR=0.89, 95%CI: 0.77-0.99) and minocycline (RR=1.22, 95%CI: 1.03-1.49). For remission, NSAIDs were more superior than placebo (RR=0.48, 95%CI: 0.27-0.79) and Omega-3 FA (RR=2.01, 95%CI: 1.09-3.90), while NACs were more favorable than placebo (RR=0.39, 95%CI: 0.13-0.99). Based on the surface under the cumulative ranking curve (SUCRA) value, corticosteroids (0.86) were the best anti-inflammatory agent for MDD patients in terms of efficacy, but the head-to-head comparisons for the efficacy of glucocorticoids and other agents were not statistically significant. As for acceptability, NSAIDs (0.81) were much better than other anti-inflammatory agents. Besides, NAC (0.80) was the best anti-inflammatory agent in the terms of remission. Conclusions: In summary, we found that corticosteroids were more superior than other agents in terms of efficacy according to the SUCRA value. However, this result must be interpreted with caution because the head-to-head comparisons for the efficacy of glucocorticoids and other agents did not reach statistical significance. NSAIDs were recommended for acceptability and NAC for remission rate.

Project description:INTRODUCTION:Major depression is a leading cause of disability and has been associated with adverse effects in older persons. While many pharmacological and non-pharmacological interventions have been shown to be effective to address major depression in older persons, there has not been a meta-analysis that consolidates all the available interventions and compare the relative benefits of these available interventions. In this study, we aim to conduct a systematic review and network meta-analysis to compare the efficacy and acceptability of all the known pharmacological and non-pharmacological interventions for major depression in older persons. METHODS AND ANALYSIS:We will search Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials and references of other review articles for articles related to the keywords of 'randomised trial', 'major depression', 'older persons' and 'treatments'. Two reviewers will independently select the eligible articles. For each included article, the two reviewers will independently extract the data and assess the risk of bias using the Cochrane revised tool for risk of bias. Bayesian network meta-analyses will be conducted to pool the depression scores (based on standardised mean difference) and the all-cause discontinuation across all included studies. The ranking probabilities for all interventions will be estimated and the hierarchy of each intervention will be summarised as surface under the cumulative ranking curve (SUCRA). Meta-regression and sub-group analyses will also be performed to evaluate the effect of study-level covariates. The quality of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION:The results will be disseminated through conference presentations and peer-reviewed publications. They will provide the consolidated evidence to inform clinicians on the best choice of intervention to address major depression in older persons. PROSPERO REGISTRATION NUMBER:CRD42017075756.

Project description:ImportancePosttraumatic stress disorder (PTSD) is a prevalent mental disorder, with a high risk of chronicity, comorbidity, and functional impairment; PTSD is complicated to treat, and the debate on the best treatment approach is ongoing.ObjectiveTo examine comparative outcomes and acceptability of psychotherapeutic and pharmacological treatments and their combinations in adults with PTSD.Data sourcesEmbase, MEDLINE, PsycINFO, Cochrane Controlled Trials Register, and PSYNDEX were searched for studies published from January 1, 1980, to February 28, 2018. Reference lists of included studies and of previously published guidelines and systematic reviews were also searched.Study selectionOf 11 417 records identified, 12 published randomized clinical trials (RCTs) comprising 922 participants, contributing 23 direct comparisons between psychotherapeutic and pharmacological treatments or their combinations were included.Data extraction and synthesisStandardized mean differences (SMDs) and odds ratios were aggregated using random-effects network and pairwise meta-analyses. Risk of bias and indirectness was rated for each study, and network confidence was rated using the Confidence in Network Meta-Analysis framework.Main outcomes and measuresThe primary outcome was the comparative benefit between 2 treatment approaches to PTSD symptom improvement, and secondary outcome was the comparative acceptability of the treatment approaches, as indicated by patient dropout rates before treatment termination.ResultsNo treatment approach was found to be superior at the end of treatment (for all, 95% CI included 0). At the last follow-up, psychotherapeutic treatments showed greater benefit than pharmacological treatments in both network (SMD, -0.83; 95% CI, -1.59 to -0.07) and pairwise (SMD, -0.63; 95% CI, -1.18 to -0.09, 3 RCTs) meta-analyses. No difference was found between combined treatments and psychotherapeutic treatments at long-term follow-up, and combined treatments were associated with better outcomes than pharmacological treatments in the network meta-analysis (SMD, -0.96; 95% CI, -1.87 to -0.04), but not in the pairwise meta-analysis, which included 2 RCTs (SMD, -1.02; 95% CI, -2.77 to 0.72). No evidence was found for differential acceptability of the 3 treatment approaches.Conclusions and relevanceThese results suggest superiority of psychotherapeutic treatments over pharmacological treatments; network, but not pairwise, meta-analyses suggest superiority of combined treatments over pharmacological treatments in improving PTSD symptom severity in the long term. The scarcity of reported long-term findings hampers definite conclusions and demonstrates the need for robust evidence from large-scaled comparative trials providing long-term follow-up data.

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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.

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