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      Efficacy, tolerability, and acceptability of bupropion for major depressive disorder: a meta-analysis of randomized–controlled trials comparison with venlafaxine

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          Abstract

          Background

          Bupropion and venlafaxine are effective antidepressants with unique pharmacological profiles.

          Objectives

          The purpose of this meta-analysis was to determine the efficacy, acceptability, and tolerability of bupropion and venlafaxine therapies for adults with major depressive disorder (MDD). The authors searched clinical trials with low risk of bias, performed from January 1985 to February 2013.

          Data sources

          The searches of MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Controlled Trials Register were conducted in February 2013. Included populations consisted of adult patients with MDD or major depression.

          Study eligible criteria, participants, and interventions

          Included studies were randomized controlled trials (RCTs) comparing bupropion and venlafaxine in adult patients with MDD and offering endpoint results relevant to: (1) severity of depression; (2) response rate; (3) remission rate; (4) overall discontinuation rate; or (5) discontinuation rate due to adverse events. Limitation of language was not utilized.

          Study appraisal and synthesis methods

          The abstracts located from the electronic databases were reviewed. The completed reports from pertinent studies were examined, and essential data were extracted. Based on the Cochrane’s bias assessment, risks of bias were assessed. Any study with two risks or more was excluded. Efficacious outcomes included the mean changed scores of rating scales for depression, overall response rates, and overall remission rates. Acceptability was determined by the overall discontinuation rates. The discontinuation rates due to adverse events were the measurement of tolerability. Relative risks (RR) and weighted mean differences or standardized mean differences with 95% confidence intervals (CI) were computed using a random effect model.

          Results

          A total of 1,117 participants in three RCTs were included. Depression rating scales used in one and two studies were the 17-item Hamilton Depression Rating Scale and the Montgomery–Asberg Depression Rating Scale, respectively. The pooled mean changed scores of the bupropion-treated group were comparable to those of the venlafaxine-treated group with standardized mean differences (95% CI) of 0.05 (−0.16 to 0.26). The overall response and remission rates were similar with the RRs (95% CI) of 0.92 (0.79–1.08) and 0.97 (0.75–1.24), respectively. The pooled overall discontinuation rate and discontinuation rate due to adverse events were not different between groups with the RRs (95% CI) of 1.00 (0.80–1.26) and 0.69 (0.44–1.10), respectively.

          Limitations

          The small number of RCTs included in the meta-analysis.

          Conclusion

          According to the limited data obtained from three RCTs, bupropion XL is as effective and tolerable as venlafaxine XR for adult patients with MDD. Further studies in this area should be conducted to confirm these findings.

          Related collections

          Most cited references 38

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          A systematic review identifies a lack of standardization in methods for handling missing variance data.

          To describe and critically appraise available methods for handling missing variance data in meta-analysis (MA). Systematic review. MEDLINE, EMBASE, Web of Science, MathSciNet, Current Index to Statistics, BMJ SearchAll, The Cochrane Library and Cochrance Colloquium proceedings, MA texts and references were searched. Any form of text was included: MA, method chapter, or otherwise. Descriptions of how to implement each method, the theoretic basis and/or ad hoc motivation(s), and the input and output variable(s) were extracted and assessed. Methods may be: true imputations, methods that obviate the need for a standard deviation (SD), or methods that recalculate the SD. Eight classes of methods were identified: algebraic recalculations, approximate algebraic recalculations, imputed study-level SDs, imputed study-level SDs from nonparametric summaries, imputed study-level correlations (e.g., for change-from-baseline SD), imputed MA-level effect sizes, MA-level tests, and no-impute methods. This work aggregates the ideas of many investigators. The abundance of methods suggests a lack of consistency within the systematic review community. Appropriate use of methods is sometimes suspect; consulting a statistician, early in the review process, is recommended. Further work is required to optimize method choice to alleviate any potential for bias and improve accuracy. Improved reporting is also encouraged.
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            Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents.

            Recent studies suggest that the treatment of major depressive disorder (MDD) with newer antidepressant drugs that simultaneously enhance norepinephrine and serotonin neurotransmission might result in higher response and remission rates than the selective serotonin reuptake inhibitors (SSRIs). The goal of our work was to compare response rates among patients with MDD treated with either of these two broad categories of antidepressant drugs. Medline/Pubmed, EMBase, clinical trial registries, program syllabi from major psychiatric meetings held since 1995, and documents from relevant pharmaceutical companies were searched for double-blind, randomized trials comparing a newer serotonergic-noradrenergic antidepressant drug (venlafaxine, duloxetine, milnacipran, mirtazapine, mianserin, or moclobemide) with an SSRI for MDD. Ninety-three trials (n = 17,036) were combined using a random-effects model. Treatment with serotonergic + noradrenergic antidepressant drugs was more likely to result in clinical response than the SSRIs (risk ratio [RR] = 1.059; response rates 63.6% versus 59.3%; p = .003). There was no evidence for heterogeneity among studies combined (p = 1.0). Excluding each individual agent did not significantly alter the pooled RR. With the exception of duloxetine (.985), RRs for response for each individual serotonergic + noradrenergic antidepressant drug were within the 95% confidence interval of the pooled RR (1.019-1.101). Serotonergic-noradrenergic antidepressant drugs seem to have a modest efficacy advantage compared with SSRIs in MDD. With the Number Needed to Treat (NNT) statistic as one indicator of clinical significance, nearly 24 patients would need to be treated with dual-action antidepressant drugs instead of SSRIs in order to obtain one additional responder. This difference falls well below the mark of NNT = 10 suggested by the United Kingdom's National Institute of Clinical Excellence but nonetheless might be of public health relevance given the large number of depressed patients treated with SSRI /serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant drugs. Further research is needed to examine whether larger differences between classes of antidepressant drugs might exist in specific MDD sub-populations or for specific MDD symptoms.
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              Measuring depression: comparison and integration of three scales in the GENDEP study.

              A number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales. The 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI) were administered to 660 adult patients with unipolar depression in a multi-centre pharmacogenetic study. Item response theory (IRT) and factor analysis were used to evaluate their psychometric properties and estimate true depression severity, as well as to group items and derive factor scores. The MADRS and the BDI provide internally consistent but mutually distinct estimates of depression severity. The HAMD-17 is not internally consistent and contains several items less suitable for out-patients. Factor analyses indicated a dominant depression factor. A model comprising three dimensions, namely 'observed mood and anxiety', 'cognitive' and 'neurovegetative', provided a more detailed description of depression severity. The MADRS and the BDI can be recommended as complementary measures of depression severity. The three factor scores are proposed for external validation.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2013
                27 September 2013
                : 7
                : 1053-1062
                Affiliations
                Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
                Author notes
                Correspondence: Benchalak Maneeton, Department of Psychiatry, Faculty of Medicine, Chiang Mai, University, 110 Intavaroros Road, Chiang Mai, Thailand, Phone +66 5 394 5422, Fax +66 5 394 5426, Email bkhongsa@ 123456med.cmu.ac.th
                Article
                dddt-7-1053
                10.2147/DDDT.S46849
                3790834
                © 2013 Maneeton et al. This work is published by Dove Medical Press Ltd, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Ltd, provided the work is properly attributed.

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                Review

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