scholarly journals Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium

2021 ◽  
pp. 026988112110135
Author(s):  
Gustavo H. Vázquez ◽  
Anees Bahji ◽  
Juan Undurraga ◽  
Leonardo Tondo ◽  
Ross J. Baldessarini
Keyword(s):  
Second Generation ◽  
Meta Analysis ◽  
Major Depressive ◽  
Combination Treatments ◽  
Second Generation Antipsychotics ◽  
Numbers Needed To Treat ◽  
Resistant Depression ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Nonpharmacological Treatments

Background: Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD include increasing antidepressant dose, combining antidepressants, adding adjunctive agents, or using nonpharmacological treatments. Their relative efficacy and tolerability remain inadequately tested. In particular, the value and safety of increasingly employed second-generation antipsychotics (SGAs) and new esketamine, compared to lithium as antidepressant adjuncts remain unclear. Methods: We reviewed randomized, placebo-controlled trials and used random-effects meta-analysis to compare odds ratio (OR) versus placebo, as well as numbers-needed-to-treat (NNT) and to-harm (NNH), for adding SGAs, esketamine, or lithium to antidepressants for major depressive episodes. Results: Analyses involved 49 drug-placebo pairs. By NNT, SGAs were more effective than placebo (NNT = 11 [CI: 9–15]); esketamine (7 [5–10]) and lithium (5 [4–10]) were even more effective. Individually, aripiprazole, olanzapine+fluoxetine, risperidone, and ziprasidone all were more effective (all NNT < 10) than quetiapine (NNT = 13), brexpiprazole (16), or cariprazine (16), with overlapping NNT CIs. Risk of adverse effects, as NNH for most-frequently reported effects, among SGAs versus placebo was 5 [4–6] overall, and highest with quetiapine (NNH = 3), lowest with brexpiprazole (19), 5 (4–6) for esketamine, and 9 (5–106) with lithium. The risk/benefit ratio (NNH/NNT) was 1.80 (1.25–10.60) for lithium and much less favorable for esketamine (0.71 [0.60–0.80]) or SGAs (0.45 [0.17–0.77]). Conclusions: Several modern antipsychotics and esketamine appeared to be useful adjuncts to antidepressants for acute major depressive episodes, but lithium was somewhat more effective and better tolerated. Limitations: Most trials of adding lithium involved older, mainly tricyclic, antidepressants, and the dosing of adjunctive treatments were not optimized.

scholarly journals Repetitive transcranial magnetic stimulation in non-treatment-resistant depression

2019 ◽  
Vol 215 (2) ◽  
pp. 445-446 ◽  
Author(s):  
Maximilian Kiebs ◽  
René Hurlemann ◽  
Julian Mutz
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Meta Analysis ◽  
Treatment Resistance ◽  
Major Depressive ◽  
Resistant Depression ◽  
Using Data ◽  
Major Depressive Episodes ◽  
Depressive Episodes

SummaryRepetitive transcranial magnetic stimulation (rTMS) has been investigated as treatment for major depressive episodes since the early 1990s. Using data from a recent meta-analysis, we show that most patients included in randomised trials display relatively high degrees of treatment resistance. This might have unfavourably biased the clinical reputation of rTMS.Declaration of interestsM.K. has received a lecture fee from Innomed Medizintechnik in 2017 and 2018.

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.

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.

scholarly journals Cariprazine as a treatment across the bipolar I spectrum from depression to mania: mechanism of action and review of clinical data

2020 ◽  
Vol 10 ◽  
pp. 204512532090575 ◽  
Author(s):  
Stephen M. Stahl ◽  
Sarah Laredo ◽  
Debbi Ann Morrissette
Keyword(s):  
Mechanism Of Action ◽  
Maintenance Treatment ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Major Depressive ◽  
Partial Agonists ◽  
Second Generation Antipsychotics ◽  
Post Hoc ◽  
Major Depressive Episodes ◽  
Depressive Episodes

Cariprazine is one of the newest dopamine-serotonin partial agonists, also known as ‘atypical’ second generation antipsychotics. Originally approved for acute and maintenance treatment of schizophrenia as well as for acute mania and mixed mania/depression, cariprazine has now been approved for bipolar I depression. Additionally, post hoc analyses of bipolar I depressed subjects show that both those with and those without concurrent manic features were improved following treatment with cariprazine. Maintenance studies are in progress in bipolar disorder, as are studies to augment antidepressants in unipolar major depressive episodes insufficiently responsive to treatment. Here, we review specifically the efficacy and safety data of cariprazine in bipolar I disorder and discuss the hypothesized mechanism of action of cariprazine and how it could theoretically be linked to caprazine’s broad therapeutic actions across the mood disorder spectrum.

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.

Efficacy of ketamine for major depressive episodes at 2, 4, and 6-weeks post-treatment: A meta-analysis

2021 ◽  
Author(s):  
Ashley A. Conley ◽  
Amber E. Q. Norwood ◽  
Thomas C. Hatvany ◽  
James D. Griffith ◽  
Kathryn E. Barber
Keyword(s):  
Meta Analysis ◽  
Post Treatment ◽  
Major Depressive ◽  
Major Depressive Episodes ◽  
Depressive Episodes
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