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Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression: An update of the 2007 Comparative Effectiveness Review [Entered Retrospectively]


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Statistics: 221 Studies, 2 Key Questions, 2 Extraction Forms,
Date Published: Jul 23, 2015 02:38PM
Description: Background: Depressive disorders such as major depressive disorder (MDD), dysthymia, and subsyndromal depression may be serious disabling illnesses. MDD affects more than 16 percent of adults at some point during their lifetimes. Second-generation antidepressants dominate the medical management of depressive disorders. These drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other drugs with related mechanisms of action that selectively target neurotransmitters. Objectives: The objective of this report was to compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of depressive disorders, including variations of effects in patients with accompanying symptoms and patient subgroups. Data Sources: We updated a comparative effectiveness review published in 2007 by the Agency for Healthcare Research and Quality searching PubMed, Embase, The Cochrane Library, and International Pharmaceutical Abstracts up to January 2011. Review Methods: Two people independently reviewed the literature, abstracted data, and rated the risk of bias. If data were sufficient, we conducted meta-analyses of head-to-head trials of the relative benefit of response to treatment. In addition, we conducted mixed treatment comparisons to derive indirect estimates of the comparative efficacy among all second-generation antidepressants. Results: From a total of 3,722 citations, we identified 248 studies of good or fair quality. Overall, no substantial differences in efficacy could be detected among second-generation antidepressants for the treatment of acute-phase MDD. Statistically significant differences in response rates between some drugs are small and likely not clinically relevant. No differences in efficacy were apparent in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbidities, although evidence within these subpopulations was limited. Differences exist in the incidence of specific adverse events and the onset of action. Venlafaxine leads to higher rates of nausea and vomiting, sertraline to higher rates of diarrhea, and mirtazapine to higher rates of weight gain than comparator drugs. Bupropion causes lower rates of sexual dysfunction than other antidepressants. The evidence is insufficient to draw conclusions about the comparative efficacy and effectiveness for the treatment of dysthymia and subsyndromal depression. Conclusions: Our findings indicate that the existing evidence does not warrant the choice of one second-generation antidepressant over another based on greater efficacy and effectiveness. Differences with respect to onset of action and adverse events may be taken into consideration for the choice of a medication.
Contributor(s): Gerald Gartlehner, MD, MPH; Richard A. Hansen, PhD; Laura C. Morgan, MA; Kylie Thaler, MD, MPH; Linda J. Lux, MPA; Megan Van Noord, MSIS; Ursula Mager, PhD, MPH; Bradley N. Gaynes, MD, MPH; Patricia Thieda, MA; Michaela Strobelberger, MA; Stacey Lloyd, MPH; Ursula Reichenpfader, MD, MPH; Kathleen N. Lohr, PhD
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We have made only a few changes to the methods used for the CER published in 2007. They involve drugs, approaches to the literature searches, articles included or excluded, techniques for quantitative synthesis, and grading strength of evidence for the overall body of evidence. Specific changes are noted here; longer documentation will be found in later parts of this methods chapter. We added one drug—desvenlafaxine—to the literature searches and analyses (we used the same search strategy in electronic databases as for the original report). For manual literature searches, we changed the process to semi-automatic searches using the ScopusTM abstraction and citation database (www.scopus.com/home.url). The method is described below in the section on Literature Searches. We did not make any changes to the eligibility criteria (Table 4 in the Introduction). We used the same approach as in the 2007 report to select literature, assess the quality of individual studies (i.e., appraise their risk for bias), and extract relevant data. Despite using identical methods to select relevant evidence, however, we removed some studies in the 2007 report from the current update. These studies had not met eligibility criteria in the 2007 report to begin with, but because they represented the only available evidence to answer a particular question at the time we had retained them. In the 2007 report we also had briefly summarized findings of such studies to provide a synopsis of the best available evidence (best- evidence approach). When, for this update, we have identified newer evidence that meets our eligibility criteria, we excluded the other "ineligible" studies from the current update. For indirect comparisons we changed our statistical methods. Specifically, we now use a Bayesian mixed-treatment comparisons approach rather than meta-regressions and network meta-analyses. A detailed description of this approach appears in the section below on Data Synthesis. We changed our method for rating the strength of evidence. In 2007 we used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. For this update, we follow the principles outlined for use by the AHRQ Evidence-based Practice Centers in AHRQ’s Methods Guide for Effectiveness and Comparative Effectiveness Reviews20 (www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and- reports/?pageaction=displayproduct&productid=318). Details are summarized below in Grading Strength of a Body of Evidence.

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Procedures for Managing Postpartum Hemorrhage: A Systematic Review


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Statistics: 73 Studies, 5 Key Questions, 2 Extraction Forms,
Date Published: Jul 23, 2015 02:37PM
Description: None Provided
Contributor(s): Nila A. Sathe, MA, MLIS Jessica Young, MD, MPH Frances E. Likis, DrPH, NP, CNM, FACNM, FAAN Daphne Carlson-Bremer, DVM. PhD Alicia Morgans, MD Jeff Andrews, MD
Funding Source: None Provided
Methodology Description: None Provided

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Pain Management Injection Therapies for Low-back Pain [Entered Retrospectively]


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Statistics: 92 Studies, 7 Key Questions, 1 Extraction Form,
Date Published: Jul 23, 2015 02:36PM
Description: Structured Abstract Objectives. Low back pain is common and injections with corticosteroids are a frequently used treatment option. This report reviews the current evidence on effectiveness and harms of epidural, facet joint, and sacroiliac corticosteroid injections for low back pain conditions. Data Sources. A prior systematic review (searches through July 2008), electronic databases (Ovid MEDLINE, Scopus, and the Cochrane Libraries from January 2008 through October 2014), reference lists, and clinical trials registries. Review Methods. Using predefined criteria, we selected randomized trials of patients with lumbosacral radiculopathy, spinal stenosis, nonradicular back pain, or chronic postsurgical back pain that compared effectiveness or harms of epidural, facet joint, or sacroiliac corticosteroid injections versus placebo or other interventions. We also included randomized trials that compared different injection techniques and large (sample sizes >1000) observational studies of back injections that reported harms. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis on outcomes stratified by immediate- (1 week to <2 weeks), short- (2 weeks to <3 months), intermediate- (3 months to <1 year), and long-term (>1 year) followup. Results. Seventy-eight randomized trials of epidural injections, 13 trials of facet joint injections, and one trial of sacroiliac injections were included. For epidural corticosteroid injections versus placebo interventions for radiculopathy, the only statistically significant effects were on mean improvement in pain at immediate-term followup (weighted mean difference [WMD] ‒7.55 on a 0 to 100 scale, 95% CI ‒11.4 to ‒3.74) (strength of evidence [SOE]: moderate), mean improvement in function at immediate-term followup when an outlier trial was excluded (standardized mean difference [SMD] ‒0.33, 95% CI ‒0.56 to ‒0.09) (SOE: low), and risk of surgery at short-term followup (relative risk [RR] 0.62, 95% CI 0.41 to 0.92) (SOE: low). The magnitude of effects on pain and function was small, did not meet predefined thresholds for minimum clinically important differences, and there were no differences on outcomes at longer-term followup. Evidence on effects of different injection techniques, patient characteristics, or comparator interventions estimates was limited and did not show clear effects. Trials of epidural corticosteroid injections for radiculopathy versus nonplacebo interventions did not clearly demonstrate effectiveness (SOE: insufficient to low). Evidence was limited for epidural corticosteroid injections versus placebo interventions for spinal stenosis (SOE: low to moderate) or nonradicular back pain (SOE: low), but showed no differences in pain, function, or likelihood of surgery. Studies found no clear differences between various facet joint corticosteroid injections (intra-articular, extra-articular [peri-capsular], or medial branch) and placebo interventions (SOE: low to moderate). There was insufficient evidence from one very small trial to determine effects of peri-articular sacroiliac joint corticosteroid injections injection (SOE: insufficient). Serious harms from injections were rare in randomized trials and observational studies, but harms reporting was suboptimal (SOE: low). Conclusions: Epidural corticosteroid injections for radiculopathy were associated with immediate improvements in pain and might be associated with immediate improvements in function, but benefits were small and not sustained, and there was no effect on long-term risk of surgery. Evidence did not suggest that effectiveness varies based on injection technique, corticosteroid, dose, or comparator. Limited evidence suggested that epidural corticosteroid injections are not effective for spinal stenosis or nonradicular back pain and that facet joint corticosteroid injections are not effective for presumed facet joint pain. There was insufficient evidence to evaluate effectiveness of sacroiliac joint corticosteroid injections.
Contributor(s): Roger Chou, MD, FACP Robin Hashimoto, PhD Janna Friedly, MD Rochelle Fu, PhD Tracy Dana, MLS Sean Sullivan, PhD Christina Bougatsos, MPH Jerry Jarvik, MD, MPH
Funding Source: Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. HHSA 290-2012-00014-I.) Rockville, MD: Agency for Healthcare Research and Quality; March 2015. www.effectivehealthcare.ahrq.gov/reports/final.cfm
Methodology Description: Review Methods. Using predefined criteria, we selected randomized trials of patients with lumbosacral radiculopathy, spinal stenosis, nonradicular back pain, or chronic postsurgical back pain that compared effectiveness or harms of epidural, facet joint, or sacroiliac corticosteroid injections versus placebo or other interventions. We also included randomized trials that compared different injection techniques and large (sample sizes >1000) observational studies of back injections that reported harms. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis on outcomes stratified by immediate- (1 week to <2 weeks), short- (2 weeks to <3 months), intermediate- (3 months to <1 year), and long-term (>1 year) followup.)

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Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update [Entered Retrospectively]


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Statistics: 176 Studies, 4 Key Questions, 4 Extraction Forms,
Date Published: Jul 23, 2015 02:36PM
Description: Objectives: Given the number of medications available for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices. The objective of this review was to summarize the benefits and harms of medications (metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 [DPP- 4] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists), as monotherapy and in combination, for the treatment of adults with type 2 diabetes; Data Sources: We searched the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from inception through April 2010 for original English-language articles and sought unpublished data from the Food and Drug Administration and others; Review Methods: Two reviewers independently screened titles to identify studies that assessed intermediate outcomes (e.g., hemoglobin A1c [HbA1c]), long-term clinical outcomes (e.g., mortality), and harms (e.g., hypoglycemia) in head-to-head monotherapy or combination therapy comparisons. Two reviewers serially extracted data for each article using standardized protocols, assessed applicability, and independently evaluated study quality; Results: The review included 140 randomized controlled trials and 26 observational studies. We graded evidence as low or insufficient for long-term clinical outcomes of all-cause mortality, cardiovascular disease, nephropathy, and neuropathy. Most medications lowered HbA1c on average by 1 absolute percentage point, but metformin was more efficacious than the DPP-4 inhibitors. Two-drug combinations had similar HbA1c reduction. Compared with metformin, thiazolidinediones and sulfonylureas had a more unfavorable effect on weight (mean difference of +2.6 kg). Metformin decreased low density lipoprotein cholesterol relative to pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a fourfold higher risk of mild/moderate hypoglycemia compared with metformin alone, and, in combination with metformin, had more than a fivefold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas and bone fractures relative to metformin. Diarrhea occurred more often for metformin compared with thiazolidinedione users; Conclusions: Comprehensive information comparing benefits and harms of diabetes medications can facilitate personalized treatment choices for patients. Although the long-term benefits and harms of diabetes medications remain unclear, the evidence supports use of metformin as a first- line agent. Comparisons of two-drug combinations showed little to no difference in HbA1c reduction, but some combinations increased risk for hypoglycemia and other adverse events.
Contributor(s): Wendy L. Bennett, MD, MPH; Lisa M. Wilson, ScM; Shari Bolen, MD, MPH; Nisa Maruthur, MD; Sonal Singh, MD; Ranee Chatterjee, MD, MPH; Spyridon S. Marinopoulos, MD, MBA; Milo A. Puhan, MD, PhD; Padmini Ranasinghe, MD, MPH; Wanda K. Nicholson, MD, MPH; Lauren Block, MD; Olaide Odelola, MBBS, MPH; Deepan S. Dalal, MBBS, MPH; Grace E. Ogbeche, MBBS, MPH; Aditya Chandrasekhar, MBBS; Susan Hutfless, PhD; Eric B. Bass, MD, MPH; Jodi B. Segal, MD, MPH
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We searched the following databases for primary studies for the periods in parentheses: MEDLINE® (1966 to April 2010), Embase® (1974 to April 2010), and the Cochrane Central Register of Controlled Trials (1966 to April 2010). We updated the MEDLINE search to December 2010 for long-term clinical outcomes (i.e., all-cause mortality, cardiovascular morbidity and mortality, nephropathy and neuropathy). We developed a search strategy for MEDLINE, accessed via PubMed, based on an analysis of the medical subject headings (MeSH) terms and text words of key articles identified a priori. Our search strategy was similar to the one used for the initial 2007 review,21 but it included terms for the additional medications included in this review (Appendix B). In addition, we received the following material from the Scientific Resource Center: • Medical reviews of rosiglitazone, pioglitazone, sitagliptin, glyburide, and metformin, combination of metformin and glipizide, combination of metformin and sitagliptin, insulin detemir, exenatide and postmarketing drug safety information on pioglitazone and insulin glargine from the FDA Web site • The Scientific Discussion sections of the European Public Assessment Reports for rosiglitazone, pioglitazone, sitagliptin, combination rosiglitazone and metformin, exenatide, insulin detemir, and insulin glargine • Health Canada Product Monographs for rosiglitazone, pioglitazone, sitagliptin, combination rosiglitazone and metformin, insulin glargine, and insulin detemir • Public registries of clinical trials, such as Clinical Study Results Web site (available at: www.clinicalstudyresults.org) and ClinicalTrials.gov (available at: www.clinicaltrials.gov). We hand searched 15 journals that most likely to publish articles on this topic (see Appendix C) by scanning the table of contents of each issue for relevant citations from February 2009 through September 2009. We also reviewed the reference lists of each included article and relevant review articles. The results of the searches were downloaded and imported into ProCite® version 5 (ISI ResearchSoft, Carlsbad, CA). We scanned for exact article duplicates, author/title duplicates, and title duplicates using the duplication check feature in ProCite.® From ProCite, the articles were uploaded to DistillerSR (Evidence Partners, Ottawa, Ontario, Canada), a Web-based software package developed for systematic review data management. This database was used to track the search results at the levels of title review, abstract review, article inclusion/exclusion, and data abstraction.

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Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies


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Statistics: 24 Studies, 2 Key Questions, 2 Extraction Forms,
Date Published: Jul 23, 2015 02:34PM
Description: The objective of this project is to systematically review and quantitatively evaluate randomized controlled trials and prospective cohort studies, separately, that examined the relationship between low-calorie sweeteners and body weight and composition.
Contributor(s): None Provided
Funding Source: Supported by funding from the North American Branch of the International Life Sciences Institute.
Methodology Description: A systematic literature search identified 15 randomized controlled trials and 9 prospective cohort studies that examined low-calorie sweeteners from foods or beverages, or low-calorie sweeteners consumed as tabletop sweeteners. Meta-analyses generated weighted mean differences in body weight and composition values between the low-calorie sweetener and control groups among randomized controlled trials, and weighted mean correlations for low-calorie sweetener intake and these parameters among prospective cohort studies.

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