scholarly journals Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of adult major depressive episodes: A systematic review and network meta-analysis of 113 randomised clinical trials

2018 ◽  
Author(s):  
Julian Mutz ◽  
Vijeinika Vipulananthan ◽  
Ben Carter ◽  
Rene Hurlemann ◽  
Cynthia H Y Fu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Stimulation ◽  
Acute Treatment ◽  
Meta Analysis ◽  
High Dose ◽  
Major Depressive ◽  
Treatment Protocols ◽  
Severity Scores ◽  
Major Depressive Episodes ◽  
Depressive Episodes

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.

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 ◽  
...  
Keyword(s):  
Brain Stimulation ◽  
Meta Analysis ◽  
High Dose ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Major Depressive ◽  
Magnetic Seizure Therapy ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Theta Burst

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.

What is the role of conventional antidepressants in the treatment of major depressive episodes with Mixed Features Specifier?

CNS Spectrums ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 120-125 ◽  
Author(s):  
Gianni L. Faedda ◽  
Ciro Marangoni
Keyword(s):  
Clinical Trials ◽  
Unipolar Depression ◽  
Preliminary Evidence ◽  
Major Depressive ◽  
Pharmacological Management ◽  
Diagnostic And Statistical Manual ◽  
Mixed Features ◽  
Effective Use ◽  
Major Depressive Episodes ◽  
Depressive Episodes

The newly introduced Mixed Features Specifier of Major Depressive Episode and Disorder (MDE/MDD) is especially challenging in terms of pharmacological management. Prior to the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the symptoms of the mixed features specifier were intradepressive hypomanic symptoms, always and only associated with bipolar disorder (BD).Intradepressive hypomanic symptoms, mostly referred to as depressive mixed states (DMX), have been poorly characterized, and their treatment offers significant challenges. To understand the diagnostic context of DMX, we trace the nosological changes and collocation of intradepressive hypomanic symptoms, and examine diagnostic and prognostic implications of such mixed features.One of the reasons so little is known about the treatment of DMX is that depressed patients with rapid cycling, substance abuse disorder, and suicidal ideation/attempts are routinely excluded from clinical trials of antidepressants. The exclusion of DMX patients from clinical trials has prevented an assessment of the safety and tolerability of short- and long-term use of antidepressants. Therefore, the generalization of data obtained in clinical trials for unipolar depression to patients with intradepressive hypomanic features is inappropriate and methodologically flawed.A selective review of the literature shows that antidepressants alone have limited efficacy in DMX, but they have the potential to induce, maintain, or worsen mixed features during depressive episodes in BD. On the other hand, preliminary evidence supports the effective use of some atypical antipsychotics in the treatment of DMX.

scholarly journals Psychotherapy for subclinical depression: meta-analysis

2014 ◽  
Vol 205 (4) ◽  
pp. 268-274 ◽  
Author(s):  
Pim Cuijpers ◽  
Sander L. Koole ◽  
Annemiek van Dijke ◽  
Miquel Roca ◽  
Juan Li ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Major Depression ◽  
Depressive Disorder ◽  
Psychological Treatment ◽  
Meta Analysis ◽  
Major Depressive ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Subclinical Depression

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.

A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes

2014 ◽  
Vol 45 (4) ◽  
pp. 693-704 ◽  
Author(s):  
A. McGirr ◽  
M. T. Berlim ◽  
D. J. Bond ◽  
M. P. Fleck ◽  
L. N. Yatham ◽  
...  
Keyword(s):  
Clinical Remission ◽  
Bipolar Depression ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Number Needed To Treat ◽  
Major Depressive ◽  
Double Blind ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Rapid Treatment

BackgroundThere is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. We aimed to assess the efficacy of ketamine in major depressive episodes.MethodWe searched EMBASE, PsycINFO, CENTRAL, and Medline from 1962 to January 2014 to identify double-blind, randomized controlled trials with allocation concealment evaluating ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The primary outcome measure was clinical remission at 24 h, 3 days and 7 days post-treatment. Analyses employed a random-effects model.ResultsData were synthesized from seven RCTs employing an intravenous infusion and one RCT employing intranasal ketamine, representing 73 subjects in parallel arms and 110 subjects in cross-over designs [n = 34 with bipolar disorder (BD), n = 149 with major depressive disorder (MDD)]. Ketamine was associated with higher rates of clinical remission relative to comparator (saline or midazolam) at 24 h [OR 7.06, number needed to treat (NNT) = 5], 3 days (OR 3.86, NNT = 6), and 7 days (OR 4.00, NNT = 6), as well as higher rates of clinical response at 24 h (OR 9.10, NNT = 3), 3 days (OR 6.77, NNT = 3), and 7 days (OR 4.87, NNT = 4). A standardized mean difference of 0.90 in favor of ketamine was observed at 24 h based on depression rating scale scores, with group comparisons revealing greater efficacy in unipolar depression compared to bipolar depression (1.07 v. 0.68). Ketamine was associated with transient psychotomimetic effects, but no persistent psychosis or affective switches.ConclusionOur meta-analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. Additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.

scholarly journals Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: Effectiveness and mood conversion rate

2016 ◽  
Vol 208 (4) ◽  
pp. 359-365 ◽  
Author(s):  
Jay D. Amsterdam ◽  
Lorenzo Lorenzo-Luaces ◽  
Irene Soeller ◽  
Susan Qing Li ◽  
Jun J. Mao ◽  
...  
Keyword(s):  
Type Ii ◽  
Short Term ◽  
Major Depressive ◽  
Bipolar Ii ◽  
Severity Scores ◽  
Bipolar Type ◽  
Antidepressant Use ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Over Time

BackgroundControversy exists over antidepressant use in bipolar II depression.AimsTo compare the safety and effectiveness of antidepressant v. mood stabiliser monotherapy for bipolar type II major depressive episodes.MethodRandomised, double-blind, parallel-group, 12-week comparison of venlafaxine (n = 65) v. lithium (n = 64) monotherapy in adult out-patients (trial registration number NCT00602537).ResultsPrimary outcome – venlafaxine produced a greater response rate (67.7%) v. lithium (34.4%, P<0.001). Secondary outcomes – venlafaxine produced a greater remission rate (58.5% v. 28.1%, P<0.001); greater decline in depression symptom scores over time (β=–5.32, s.e. = 1.16, χ2 = 21.19, P<0.001); greater reduction in global severity scores over time (β=–1.05, s.e. = 0.22, χ2 = 22.33, P<0.001); and greater improvement in global change scores (β=–1.31, s.e. = 0.32, χ2 = 16.95, P<0.001) relative to lithium. No statistically significant or clinically meaningful differences in hypomanic symptoms were observed between treatments.ConclusionsThese findings suggest that short-term venlafaxine monotherapy may provide effective antidepressant treatment for bipolar II depression without a statistically significant increase in hypomanic symptoms relative to lithium.

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