scholarly journals 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

2019 ◽  
Vol 22 (11) ◽  
pp. 698-709
Author(s):  
Taro Kishi ◽  
Kenji Sakuma ◽  
Ikuo Nomura ◽  
Yuki Matsuda ◽  
Kazuo Mishima ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Scale Score ◽  
Response Rate ◽  
Meta Analysis ◽  
Weight Increase ◽  
Adjunctive Treatment ◽  
Number Needed To Treat ◽  
Major Depressive ◽  
Severity Scores

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.

scholarly journals Is transcranial direct current stimulation, alone or in combination with antidepressant medications or psychotherapies, effective in treating major depressive disorder? A systematic review and meta-analysis

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingying Wang ◽  
Huichun Luo ◽  
Rasmus Schülke ◽  
Xinyi Geng ◽  
Barbara J. Sahakian ◽  
...  
Keyword(s):  
Systematic Review ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Sham Group ◽  
Response Rate ◽  
Meta Analysis ◽  
Depression Score ◽  
Major Depressive ◽  
Remission Rates ◽  
Meta Regression

Abstract Background Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. The efficacies of tDCS combination therapies have not been investigated deliberately. This review aims to evaluate the clinical efficacy of tDCS as a monotherapy and in combination with medication, psychotherapy, and ECT for treating adult patients with major depressive disorder (MDD) and identified the factors influencing treatment outcome measures (i.e. depression score, dropout, response, and remission rates). Methods The systematic review was performed in PubMed/Medline, EMBASE, PsycINFO, Web of Sciences, and OpenGrey. Two authors performed independent literature screening and data extraction. The primary outcomes were the standardized mean difference (SMD) for continuous depression scores after treatment and odds ratio (OR) dropout rate; secondary outcomes included ORs for response and remission rates. Random effects models with 95% confidence intervals were employed in all outcomes. The overall effect of tDCS was investigated by meta-analysis. Sources of heterogeneity were explored via subgroup analyses, meta-regression, sensitivity analyses, and assessment of publication bias. Results Twelve randomised, sham-controlled trials (active group: N = 251, sham group: N = 204) were included. Overall, the integrated depression score of the active group after treatment was significantly lower than that of the sham group (g = − 0.442, p = 0.017), and further analysis showed that only tDCS + medication achieved a significant lower score (g = − 0.855, p < 0.001). Moreover, this combination achieved a significantly higher response rate than sham intervention (OR = 2.7, p = 0.006), while the response rate remained unchanged for the other three therapies. Dropout and remission rates were similar in the active and sham groups for each therapy and also for the overall intervention. The meta-regression results showed that current intensity is the only predictor for the response rate. None of publication bias was identified. Conclusion The effect size of tDCS treatment was obviously larger in depression score compared with sham stimulation. The tDCS combined selective serotonin re-uptake inhibitors is the optimized therapy that is effective on depression score and response rate. tDCS monotherapy and combined psychotherapy have no significant effects. The most important parameter for optimization in future trials is treatment strategy.

Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: systematic review and meta-analysis

2013 ◽  
Vol 44 (11) ◽  
pp. 2255-2269 ◽  
Author(s):  
T. Kishi ◽  
H. Y. Meltzer ◽  
Y. Matsuda ◽  
N. Iwata
Keyword(s):  
Systematic Review ◽  
Major Depressive Disorder ◽  
Side Effects ◽  
Depressive Disorder ◽  
Partial Agonist ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Cochrane Library ◽  
Number Needed To Treat ◽  
Major Depressive

BackgroundA meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported.MethodWe carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95% confidence intervals (CIs).ResultsFifteen RCTs comparing 5-HT1A agonists with placebo (total n = 2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95% CI 0.65–083, p < 0.00001, NNT = 6, 12 trials, n = 1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p = 0.02, NNH = 16, p = 0.03, 10 trials, n = 1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p < 0.0001, NNH = 17, p = 0.001, 13 trials, n = 2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p = 0.85, 14 trials, n = 2402). Four 5-HT1A agonist augmentation studies were identified (total n = 365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p = 0.85, four trials, n = 341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p < 0.00001 to p = 0.03).ConclusionsOur results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

Examining the Evidence on Augmentation with Atypical Antipsychotics

CNS Spectrums ◽  
2007 ◽  
Vol 12 (S22) ◽  
pp. 10-12
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Atypical Antipsychotics ◽  
Response Rate ◽  
Meta Analysis ◽  
Response Rates ◽  
Controlled Trials ◽  
Major Depressive ◽  
Double Blind ◽  
Double Blind Placebo

There is mounting evidence to suggest that the efficacy of all available antidepressants when used as monotherapy to treat major depressive disorder (MDD) is, at best, modest. For example, a meta-analysis of all double-blind placebo-controlled studies of antidepressants published since 1980 revealed response rates of 53% for antidepressants versus 36% for placebo (difference in response rate of 16.8%) (Slide 1). To make matters worse, if one is to assume that “negative trials” (ie, trials which do not demonstrate the superiority of a drug over placebo) are less likely to be published than “positive trials” (trials which demonstrate the superiority of a drug versus placebo), it is quite possible that the margin of efficacy of antidepressants when compared to placebo is ≤16.8%. Thus, if one were to include all unpublished along with published double-blind, placebo-controlled trials of antidepressants for MDD, this efficacy margin could be ≤10%.

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