Dataset Information

Brexpiprazole as Adjunctive Treatment for Major Depressive Disorder Following Treatment Failure With at Least One Antidepressant in the Current Episode: a Systematic Review and Meta-Analysis.

ABSTRACT:

Background

This systematic review and meta-analysis included double-blind, randomized, placebo-controlled trials of brexpiprazole adjunctive treatment (0.5-3 mg/d) for major depressive disorder where antidepressant treatment had failed.

Methods

The outcomes were the response rate (primary), remission rate (secondary), Montgomery Åsberg Depression Rating Scale score (secondary), Sheehan Disability Scale scores (secondary), Clinical Global Impression-Improvement/Severity scores, discontinuation rate, and individual adverse events. A subgroup meta-analysis of the data at week 6 compared outcomes by dose >2 mg/d or ≤2 mg/d (2 mg/d is the recommended dose).

Results

We identified 9 studies (n = 3391). Compared with placebo, brexpiprazole (any dose) was superior for response rate (risk ratio [RR] = 0.93, 95% confidence interval [95% CI] = 0.89-0.97, number needed to treat = 17), remission rate (RR = 0.95, 95% CI = 0.93-0.98, number needed to treat = 25), Montgomery Åsberg Depression Rating Scale score (standardized mean difference = -0.20, 95% CI = -0.29, -0.11), Sheehan Disability Scale score (standardized mean difference = -0.12, 95% CI = -0.21, -0.04), and Clinical Global Impression-Improvement/Severity scores but was associated with a higher discontinuation rate, akathisia, insomnia, restlessness, somnolence, and weight increase. Doses >2 mg/d had a significantly higher RR for response rate than ≤2 mg/d (0.96 vs 0.89); moreover, compared with placebo, doses >2 mg/d were associated with higher incidences of akathisia (RR = 4.58) and somnolence (RR = 7.56) as well as were marginally associated with a higher incidence of weight increase (RR = 3.14, P = .06). Compared with placebo, doses ≤2 mg/d were associated with higher incidences of akathisia (RR = 2.28) and weight increase (RR = 4.50).

Conclusions

Brexpiprazole adjunctive treatment is effective for major depressive disorder when antidepressant treatment fails. At 6 weeks, doses ≤2 mg/d presented a better risk/benefit balance than >2 mg/d.

SUBMITTER: Kishi T

PROVIDER: S-EPMC6872963 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Brexpiprazole as Adjunctive Treatment for Major Depressive Disorder Following Treatment Failure With at Least One Antidepressant in the Current Episode: a Systematic Review and Meta-Analysis.

Kishi Taro T Sakuma Kenji K Nomura Ikuo I Matsuda Yuki Y Mishima Kazuo K Iwata Nakao N

The international journal of neuropsychopharmacology 20191101 11

<h4>Background</h4>This systematic review and meta-analysis included double-blind, randomized, placebo-controlled trials of brexpiprazole adjunctive treatment (0.5-3 mg/d) for major depressive disorder where antidepressant treatment had failed.<h4>Methods</h4>The outcomes were the response rate (primary), remission rate (secondary), Montgomery Åsberg Depression Rating Scale score (secondary), Sheehan Disability Scale scores (secondary), Clinical Global Impression-Improvement/Severity scores, dis ...[more]

PMID: 31350882

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Project description:BackgroundApproximately 50% of patients with major depressive disorder do not respond adequately to their antidepressant treatment, underscoring the need for more effective treatment options. The objective of this study was to investigate the effect of adjunctive brexpiprazole on depressive symptoms in patients with major depressive disorder who were not responding to adjunctive or combination therapy of their current antidepressant treatments with several different classes of agents (NCT02012218).MethodsIn this 6-week, open-label, phase 3b study, patients with major depressive disorder who had an inadequate response to ≥1 adjunctive or combination therapy, in addition to history of ≥1 failure to monotherapy antidepressant treatment, were switched to adjunctive brexpiprazole. Efficacy was assessed by change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale total score. Patient functioning was assessed using the Sheehan Disability Scale and the Cognitive and Physical Functioning Questionnaire. Safety and tolerability were also assessed.ResultsA total of 51/61 (83.6%) patients completed 6 weeks of treatment with adjunctive brexpiprazole. Improvements in depressive symptoms were observed (least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale total score, -17.3 [P < .0001]) as well as improvements in general and cognitive functioning (mean changes from baseline to week 6: Sheehan Disability Scale, -3.1 [P < .0001]; Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire, -9.2 [P < .0001]). The most common adverse event was fatigue (14.8%); akathisia was reported by 8.2% of patients.ConclusionsIn patients with major depressive disorder who had switched to open-label adjunctive brexpiprazole following inadequate response to previous adjunctive or combination therapy, improvements were observed in depressive symptoms, general functioning, cognitive function, and energy/alertness.

Project description:ObjectiveEpisodes of major depressive disorder (MDD) characterized by high levels of anxiety symptoms are less likely to respond to some forms of antidepressant treatment (ADT). This report examines the effects of adjunctive brexpiprazole on depressive symptoms among patients with MDD and anxiety symptoms.Materials and methodsThis was a post hoc analysis of 1,171 patients from the 6-week, randomized, double-blind phases of three studies in adults with MDD and inadequate response to ADTs (NCT01360645, NCT01360632, NCT02196506). Data were pooled for brexpiprazole 2-3 mg/day and for placebo (adjunct to ADT). Montgomery-Åsberg Depression Rating Scale Total score changes were assessed in subgroups of patients with and without anxious distress (based on proxies for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria) and anxious depression (defined as a Hamilton Depression Rating Scale Anxiety/somatization factor score of ≥7). Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs).ResultsBenefits were seen for adjunctive brexpiprazole (compared with adjunctive placebo) in both anxiety definition subgroups. For patients with anxious distress, the least squares mean difference (95% CI) at week 6 was -3.00 (-4.29, -1.71; P<0.0001) and, for those without anxious distress, was -1.38 (-2.71, -0.05; P=0.043). For patients with anxious depression, the difference was -2.19 (-3.60, -0.78; P=0.0023), compared with -2.34 (-3.58, -1.10; P=0.0002) for those without anxious depression. The most common TEAEs among patients with anxiety symptoms receiving ADT + brexpiprazole were akathisia, headache, restlessness, somnolence, and weight increase. There were no clinically meaningful differences in the rates of these TEAEs according to the presence or absence of anxiety symptoms.ConclusionAdjunctive brexpiprazole 2-3 mg/day may be efficacious in reducing depressive symptoms, and was well tolerated, in patients with clinically relevant anxiety symptoms.

Project description:ImportanceTranscranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective.ObjectiveTo determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode.Design, setting, and participantsThis was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications.InterventionstDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing.Main outcomes and measuresChange in HDRS-17 score at week 6.ResultsOf 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group.Conclusions and relevanceUnsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial.Trial registrationClinicalTrials.gov Identifier: NCT04889976.

Dataset Information

Brexpiprazole as Adjunctive Treatment for Major Depressive Disorder Following Treatment Failure With at Least One Antidepressant in the Current Episode: a Systematic Review and Meta-Analysis.

Background

Methods

Results

Conclusions

Publications

Brexpiprazole as Adjunctive Treatment for Major Depressive Disorder Following Treatment Failure With at Least One Antidepressant in the Current Episode: a Systematic Review and Meta-Analysis.

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