Gerald Gartlehner

Perinatal depression: a systematic review of prevalence and incidence.

OBJECTIVE: We systematically review evidence on the prevalence and incidence of perinatal depression and compare these rates with those of depression in women at nonchildbearing times. DATA SOURCES: We searched MEDLINE, CINAHL, PsycINFO, and Sociofile for English-language articles published from 1980 through March 2004, conducted hand searches of bibliographies, and consulted with experts. METHODS OF STUDY SELECTION: We included cross-sectional, cohort, and case-control studies from developed countries that assessed women for depression during pregnancy or the first year postpartum with a structured clinical interview. TABULATION, INTEGRATION, AND RESULTS: Of the 109 articles reviewed, 28 met our inclusion criteria. For major and minor depression (major depression alone), the combined point prevalence estimates from meta-analyses ranged from 6.5% to 12.9% (1.0-5.6%) at different trimesters of pregnancy and months in the first postpartum year. The combined period prevalence shows that as many as 19.2% (7.1%) of women have a depressive episode (major depressive episode) during the first 3 months postpartum; most of these episodes have onset following delivery. All estimates have wide 95% confidence intervals, showing significant uncertainty in their true levels. No conclusions could be made regarding the relative incidence of depression among pregnant and postpartum women compared with women at nonchildbearing times. CONCLUSION: To better delineate periods of peak prevalence and incidence for perinatal depression and identify high risk subpopulations, we need studies with larger and more representative samples.

Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis

Context Which disease-modifying antirheumatic drugs (DMARDs) best reduce symptoms, improve function, and prevent radiographic progression in patients with rheumatoid arthritis? Contribution This systematic review of trials that compared DMARDs in adults with rheumatoid arthritis found few direct comparisons of different agents but no important differences among synthetic DMARDs or antitumor necrosis factor drugs. Combination therapy improved response rates and functional outcomes in patients whose monotherapy failed. Numbers and types of short-term adverse events were similar among DMARDs. Implication Of several monotherapies for adults with rheumatoid arthritis, no regimen is clearly superior. Combination therapies improve response rates in some patients previously receiving monotherapy. The Editors Rheumatoid arthritis is an autoimmune disease that affects more than 2 million adults in the United States. Disease onset generally occurs between 30 and 55 years of age, and women are affected more often than men. Disease hallmarks are inflammation of the synovium, progressive bone erosion, joint malalignment and destruction, and subsequent weakness of surrounding tissues and muscles. Presentations range from mild to severe, although the typical patient has a progressive course leading to functional limitations. Treatment aims at controlling pain and inflammation and slowing or arresting the progression of joint destruction. Therapies generally used in the United States include corticosteroids; synthetic disease-modifying antirheumatic drugs (DMARDs), such as hydroxychloroquine, leflunomide, methotrexate, and sulfasalazine; and biological DMARDs, such as abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab. The American College of Rheumatology (ACR) recommends beginning DMARD therapy within 3 months of diagnosis (1). Often, treatment with a single DMARD does not adequately control symptoms, leading clinicians to consider various combination strategies. Experts do not agree about the comparative benefits of different combination therapies. Many questions remain about the risks of these agents across a spectrum of adverse events from relatively minor side effects to severe and possibly life-threatening problems. Given this uncertainty, the Agency for Healthcare Research and Quality (AHRQ) commissioned a systematic review to compare the benefits and safety of rheumatoid arthritis drugs (2). Methods We developed and followed a standardized protocol for all steps of the review. The full technical report (2) describes study methods in detail and gives evidence tables of individual studies. Literature Search We searched MEDLINE, EMBASE, The Cochrane Library, and the International Pharmaceutical Abstracts for studies from 1980 to September 2007. Search terms included Medical Subject Headings or keywords when appropriate. We combined terms for rheumatoid arthritis with 11 drugs of interest (corticosteroid, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, etanercept, infliximab, adalimumab, abatacept, anakinra, and rituximab). We limited electronic searches to studies involving adults and humans and studies in English. We manually searched reference lists of review articles and letters to the editor. In addition, we searched the Center for Drug Evaluation and Research database (September 2007) to identify unpublished research submitted to the U.S. Food and Drug Administration. In early to mid-2006, the Oregon Scientific Resource Center invited pharmaceutical manufacturers to submit dossiers on all published and unpublished studies on a specific drug. Five companies (Abbott, Amgen, Bristol-Myers Squibb, Centocor, and Genentech) provided dossiers. Study Selection Two persons, each blinded to the others results, independently reviewed titles, abstracts, and sometimes full text to identify studies meeting preestablished criteria. To assess efficacy regarding symptoms, quality of life, functional capacity, and radiographic progression, we included head-to-head controlled trials and prospective cohort studies comparing any of the therapies. For harms (specific adverse events, rates of adverse events, and discontinuation attributable to adverse events) and subgroups, we also examined data from retrospective observational studies and placebo-controlled trials. For efficacy and harm data, we selected studies with 100 or more participants and at least 12 weeks of follow-up. Finally, if we found no evidence about efficacy from direct head-to-head comparison studies, we included evidence from fair- or good-quality meta-analyses that indirectly compared placebo-controlled trial data across drugs. Data Abstraction and Quality Assessment Trained reviewers abstracted each study by using a Web-based system (SRS 4.0, TrialStat, Ottawa, Ontario, Canada). A senior reviewer read each abstracted article and evaluated completeness of data extraction. We recorded intention-to-treat results if available. We assessed the internal validity (quality) of trials on the basis of predefined criteria from the U.S. Preventive Services Task Force (rating of good, fair, or poor) (3) and the National Health Service Centre for Reviews and Dissemination (4). Elements of internal validity for trials included randomization, allocation concealment, similarity of compared groups at baseline, intention-to-treat analysis, and overall and differential loss to follow-up. To assess the quality of observational studies, we used criteria outlined by Deeks and colleagues (5). Items assessed included sample selection, adjustment for confounders, methods of outcomes assessment, length of follow-up, and statistical analysis. Data Synthesis We primarily synthesized the literature qualitatively; we reported some quantitative syntheses from fair- to good-quality meta-analyses. Drug comparisons that were not quantitatively analyzed in meta-analyses had insufficient data or noncomparable study samples and did not merit additional quantitative analyses. We examined data within 3 main drug classes (corticosteroids, synthetic DMARDs, and biological DMARDs) and between drug classes and combination therapies. Strength of Evidence Ratings We rated the strength of the available evidence in a 3-part hierarchy (high, moderate, and low) (2) based on a modified Grading of Recommendations, Assessment, Development, and Evaluation approach (6, 7). Grades reflect the strength of evidence for a given comparison with respect to specific outcomes, such as 20% improvement in ACR response criteria (ACR 20), radiographic changes, or adverse events. Role of the Funding Source Agency for Healthcare Research and Quality staff participated in formulating initial study questions and reviewed methods, data analysis, and the draft report. The funding source did not participate in the literature search, determination of study eligibility, or evaluation of individual studies. Results Characteristics of Reviewed Studies We identified 2395 citations (Figure). Working from 635 articles retrieved for full review, we included 143 published articles reporting on 101 studies (Table 1). Of the 101 included studies, 49 (48.5%) were supported by pharmaceutical companies, 20 (19.8%) by governmental or independent funds, and 11 (10.9%) by a combination of pharmaceutical and governmental funding. We could not determine the source of support for 21 (20.8%) studies. Table 1. Summary of Head-to-Head Reviewed Studies, by Drug Comparison* Figure. Study flow diagram. Numbers of included articles and included studies differ because some studies have multiple publications. RCT = randomized, controlled trial. Comparative Effectiveness and Harms We found few fair- or good-quality head-to-head trials for each drug comparison (Table 1). Most trials were efficacy trials in highly selected populations with few comorbid conditions. Most trials used ACR 20, disease activity scores to measure clinical improvement, and Sharp or Sharpvan der Heijde scores to measure radiologic progression of the disease. Trials examining quality of life used the Health Assessment Questionnaire (HAQ) or Medical Outcomes Study Short Form 36 (SF-36). Table 2 summarizes results. Table 2. Summary of Comparative Findings on Efficacy and Harms of Rheumatoid Arthritis Drugs Monotherapy versus Monotherapy Synthetic DMARDs One good systematic review that included a meta-analysis of 2 trials suggested that more patients receiving methotrexate achieved ACR 20 at 1 year than did patients receiving leflunomide (odds ratio, 1.43 [95% CI, 1.15 to 1.77]). The ACR 20 benefit was lower and more uncertain at 2 years (odds ratio, 1.28 [CI, 0.98 to 1.67]) (8). However, patients receiving methotrexate showed less improvement in health-related quality of life than did patients receiving leflunomide (odds ratio for SF-36 physical component, 3.00 [CI, 5.41 to 0.59]). Radiographic outcomes over 2 years seemed similar. For leflunomide versus sulfasalazine, data are limited to 1 trial (9) involving 358 participants with 2-year follow-up (10, 11). Leflunomide yielded more patients achieving ACR 20, ACR 50, and greater improvement in functional capacity (ACR 20, 82% vs. 60% [P= 0.008]; ACR 50, 52% vs. 25% [P= 0.040]; HAQ, 0.50 vs. 0.29 [P 0.030]). Radiographic changes were similar for the 2 drugs (Larsen score change at 2 years, 0.010 for either drug) (9). Three trials involving 479 participants and lasting up to 52 weeks compared methotrexate with sulfasalazine and found similar response rates in ACR 20, disease activity scores, or functional capacity (1214). Two trials included patients with disease for longer than 1 year and used a lower dose of weekly methotrexate (7.5 mg) than that generally used in the United States (13, 14). The overall attrition rate for these studies ranged from 19% to 28.5%. We found no statistically significant differences in frequency of serious adverse events for leflunomide, methotrexate, and sulfasalazine in 3 efficacy trial

Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder

Context The relative benefits and harms of newer, second-generation antidepressants are sometimes confusing. Contribution In this review of 46 head-to-head randomized trials, the authors generally found no major differences in the numbers of adults with major depression who responded to second-generation antidepressants, such as selective serotonin reuptake inhibitors, bupropion, duloxetine, mirtazapine, and venlafaxine. The overall incidence of adverse events appeared similar across drugs, although types of adverse events varied. Cautions Trials were funded by industry and had variable quality and follow-up duration. Implications Second-generation antidepressants generally have similar benefits but different possible harms for adults with major depression. The Editors Major depressive disorder is a serious disabling illness that affects more than 16% of adults in the United States at some point in their lifetime (1). In 2000, the economic burden of depressive disorders in the United States was estimated to be

Conducting quantitative synthesis when comparing medical interventions: AHRQ and the Effective Health Care Program

83.1 billion (2). Current practice guidelines for the treatment of major depressive disorder recommend pharmacotherapy, psychotherapy, psychotherapy plus pharmacotherapy, or electroconvulsive therapy. In most cases, pharmacotherapy is first-line treatment for major depressive disorder. Moreover, it is a practical tool for primary care physicians, who prescribe the majority of antidepressants in the United States (3). Pharmacologic treatment for major depressive disorder includes first-generation antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors) and second-generation antidepressants. Second-generation medications include selective serotonin reuptake inhibitors (SSRIs); selective norepinephrine reuptake inhibitors; and other drugs that selectively affect the activity of neurotransmitters, such as serotonin, norepinephrine, and dopamine. In general, the efficacy of first- and second-generation antidepressant medications is similar (4-6). However, first-generation antidepressants often cause multiple side effects that many patients find intolerable (7-9), and the risk for harm when taken in overdose or in combination with certain medications is high. Because of their relatively favorable side effect profile, the second-generation antidepressants play a prominent role in the management of patients with major depressive disorder. Reviews have compared the efficacy and tolerability of newer second-generation antidepressants with those of placebo or older treatments (6, 10, 11) but did not evaluate comparative evidence for second-generation antidepressants. We therefore sought to systematically evaluate comparative data on the efficacy, effectiveness, and tolerability of commonly prescribed second-generation antidepressants. Specifically, we conducted a systematic review and meta-analysis of comparative evidence for 6 SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) and 4 other second-generation antidepressants (bupropion, duloxetine, mirtazapine, and venlafaxine). From here on, we refer to these agents collectively as antidepressants. We examine the role of these agents in the initial treatment of ambulatory adult patients with major depressive disorder. Methods Key Questions Key questions designed to address the comparative efficacy, effectiveness, safety, and tolerability of antidepressants guided our research. A consortium of 12 state Medicaid programs, the Canadian Coordinating Office for Health Technology Assessment, the California HealthCare Foundation, and key experts formulated the questions and provided funding for this research. Literature Search To identify articles relevant to each key question, we searched MEDLINE, EMBASE, and PsychLit; the Cochrane Library; and the International Pharmaceutical Abstracts. To capture articles relevant to the scope of our topic, our searches covered 1980 through 28 February 2005. We manually searched reference lists of relevant review articles and letters to the editor. Pharmaceutical manufacturers were invited to submit dossiers, including citations, as outlined by the Drug Effectiveness Review Project (12). We requested unpublished studies from the U.S. Food and Drug Administration, but this agency did not release unpublished data. Study Selection Two persons independently reviewed titles and abstracts. If both reviewers agreed that a trial did not meet preestablished eligibility criteria (Appendix Table), we excluded it. To assess efficacy and effectiveness, we included head-to-head trials comparing one antidepressant with another. We defined effectiveness trials as those that were conducted in primary care settings, had an adequate duration of follow-up (3 months), had minimal inclusion and exclusion criteria (so that participants represented the general population), assessed health outcomes rather than intermediate outcomes, and had an adequate sample size to determine a minimally important difference (from a patients perspective) on a health-related quality of life instrument (13). To assess safety and tolerability, we included head-to-head trials, placebo-controlled trials, and observational studies with large samples (>100 patients) lasting at least 1 year. We required a larger sample size for observational studies because we wanted primarily to detect adverse events that were not frequent enough to be apparent in smaller trials. Data Abstraction and Quality Assessment Trained reviewers abstracted data from each study, and a senior reviewer read each abstracted article and evaluated completeness of data extraction. We recorded intention-to-treat results if they were available. We assessed the internal validity (quality) of trials by using predefined criteria from the U.S. Preventive Services Task Force (ratings of good, fair, or poor) (14) and the National Health Service Centre for Reviews and Dissemination (15). Elements of internal validity assessment included randomization, allocation concealment, similarity of compared groups at baseline, use of intention-to-treat analysis, and overall and differential loss to follow-up. We defined loss to follow-up as the number of persons who underwent randomization but did not complete the study (16), independent of the reason and whether intention-to-treat analysis was used. We rated studies as poor if they had more than 40% overall loss to follow-up or more than 15 percentage points of differential loss to follow-up between study groups. Data Synthesis We first qualitatively summarized the studies. When more than 3 head-to-head trials compared the same treatments, we did quantitative analyses. In these, the primary outcome measure was treatment response, defined as 50% or greater improvement on the Hamilton Rating Scale for Depression (HAM-D) or the MontgomeryAsberg Depression Rating Scale from baseline to study end. The relative benefit reflects the ratio of benefits or risks in one treatment group compared with another. When treatment effects differed between studies, we explored potential reasons for these differences. For each meta-analysis, we tested for heterogeneity of treatment effects by using I2 statistics. If no heterogeneity was detected, we applied both a random-effects and a fixed-effects model. We report the results of the more conservative random-effects models (17) because the validity of tests of heterogeneity can be limited with a small number of component studies. To estimate possible publication bias caused by the tendency of published studies to be positive, we used funnel plots, the Begg adjusted rank correlation test (18), and the Egger regression approach (19). However, because these tests have low statistical power when the number of trials is small (20), undetected bias may still be present. All statistical analyses were conducted by using StatsDirect Statistical Software, version 2.3.8 (StatsDirect, Ltd., Sale, United Kingdom). We calculated the mean incidence and 95% CIs for specific adverse events reported in included trials. Because assessment and reporting of adverse events varied greatly among trials, this evidence should be interpreted with caution. Role of the Funding Sources The funding sources contributed to the development of the key questions but had no role in the conduct or reporting of the study or in the decision to submit the manuscript for publication. Results We found 820 unduplicated citations. Manual review of the reference lists of pertinent review articles produced another 74 articles. Although 6 pharmaceutical companies submitted dossiers, no included studies stemmed from the dossiers. Therefore, 894 citations were included in our database (Appendix Figure). Forty-six randomized, controlled trials compared the effectiveness or efficacy of one SSRI or other antidepressant with that of another in the treatment of major depressive disorder (Tables 1 and 2). (Complete evidence tables are available at www.ohsu.edu/drugeffectiveness/reports/final.cfm or from the authors.) Most studies were efficacy trials and received a rating of fair for internal validity; some trials rated fair may have fulfilled all quality criteria but did not report methods to an extent that answered all of our questions. We considered 2 trials from Europe (21, 22) and 1 trial from the United States (23) conducted in primary care settings to be effectiveness trials. Sixty percent of included trials were less than 12 weeks in duration. The samples consisted mostly of persons younger than 60 years of age; samples consisted of persons 60 years of age or older in 6 trials (13%) and children or adolescents younger than 18 years of age in 3 trials (7%). Although sponsorship did not influence our quality rating, it may have influenced reporting. About 85% of trials in our review were sponsored by a pharmaceutical company, and an additional 11% had at least 1 author affiliated with a pharmaceutical company. The remaining 4% of included studies

The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses

OBJECTIVE This article is to establish recommendations for conducting quantitative synthesis, or meta-analysis, using study-level data in comparative effectiveness reviews (CERs) for the Evidence-based Practice Center (EPC) program of the Agency for Healthcare Research and Quality. STUDY DESIGN AND SETTING We focused on recurrent issues in the EPC program and the recommendations were developed using group discussion and consensus based on current knowledge in the literature. RESULTS We first discussed considerations for deciding whether to combine studies, followed by discussions on indirect comparison and incorporation of indirect evidence. Then, we described our recommendations on choosing effect measures and statistical models, giving special attention to combining studies with rare events; and on testing and exploring heterogeneity. Finally, we briefly presented recommendations on combining studies of mixed design and on sensitivity analysis. CONCLUSION Quantitative synthesis should be conducted in a transparent and consistent way. Inclusion of multiple alternative interventions in CERs increases the complexity of quantitative synthesis, whereas the basic issues in quantitative synthesis remain crucial considerations in quantitative synthesis for a CER. We will cover more issues in future versions and update and improve recommendations with the accumulation of new research to advance the goal for transparency and consistency.

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis

OBJECTIVE We evaluated the inter-rater reliability (IRR) of assessing the quality of evidence (QoE) using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. STUDY DESIGN AND SETTING On completing two training exercises, participants worked independently as individual raters to assess the QoE of 16 outcomes. After recording their initial impression using a global rating, raters graded the QoE following the GRADE approach. Subsequently, randomly paired raters submitted a consensus rating. RESULTS The IRR without using the GRADE approach for two individual raters was 0.31 (95% confidence interval [95% CI] = 0.21-0.42) among Health Research Methodology students (n = 10) and 0.27 (95% CI = 0.19-0.37) among the GRADE working group members (n = 15). The corresponding IRR of the GRADE approach in assessing the QoE was significantly higher, that is, 0.66 (95% CI = 0.56-0.75) and 0.72 (95% CI = 0.61-0.79), respectively. The IRR further increased for three (0.80 [95% CI = 0.73-0.86] and 0.74 [95% CI = 0.65-0.81]) or four raters (0.84 [95% CI = 0.78-0.89] and 0.79 [95% CI = 0.71-0.85]). The IRR did not improve when QoE was assessed through a consensus rating. CONCLUSION Our findings suggest that trained individuals using the GRADE approach improves reliability in comparison to intuitive judgments about the QoE and that two individual raters can reliably assess the QoE using the GRADE system.

Comparative risk for harms of second-generation antidepressants : a systematic review and meta-analysis.

OBJECTIVE To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) and 2 or more prior antidepressant treatment failures (often referred to as treatment-resistant depression [TRD]). These patients are less likely to recover with medications alone and often consider nonpharmacologic treatments such as rTMS. DATA SOURCES We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and the International Pharmaceutical Abstracts for studies comparing rTMS with a sham-controlled treatment in TRD patients ages 18 years or older. STUDY SELECTION We included 18 good- or fair-quality TRD studies published from January 1, 1980, through March 20, 2013. DATA EXTRACTION We abstracted relevant data, assessed each studys internal validity, and graded strength of evidence for change in depressive severity, response rates, and remission rates. RESULTS rTMS was beneficial compared with sham for all outcomes. rTMS produced a greater decrease in depressive severity (high strength of evidence), averaging a clinically meaningful decrease on the Hamilton Depression Rating Scale (HDRS) of more than 4 points compared with sham (mean decrease = -4.53; 95% CI, -6.11 to -2.96). rTMS resulted in greater response rates (high strength of evidence); those receiving rTMS were more than 3 times as likely to respond as patients receiving sham (relative risk = 3.38; 95% CI, 2.24 to 5.10). Finally, rTMS was more likely to produce remission (moderate strength of evidence); patients receiving rTMS were more than 5 times as likely to achieve remission as those receiving sham (relative risk = 5.07; 95% CI, 2.50 to 10.30). Limited evidence and variable treatment parameters prevented conclusions about which specific treatment options are more effective than others. How long these benefits persist remains unclear. CONCLUSIONS For MDD patients with 2 or more antidepressant treatment failures, rTMS is a reasonable, effective consideration.

Efficacy and Safety of Inhaled Corticosteroids in Patients With COPD: A Systematic Review and Meta-Analysis of Health Outcomes

Background: Evidence indicates that only minor differences in efficacy exist among second-generation antidepressants for the treatment of major depressive disorder (MDD). However, a comprehensive assessment of both benefits and harms is crucial to evaluate the net benefit.Objective: To review systematically the comparative harms of second-generation antidepressants for the treatment of MDD in adults by including both experimental and observational evidence.Data sources: We searched MEDLINE®, EMBASE, PsychLit, The Cochrane Library and the International Pharmaceutical Abstracts from 1980 to April 2007. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database to identify unpublished research.Study selection: Eligible study designs were trials and observational studies comparing one drug of interest with another.Data extraction: Two persons independently reviewed abstracts and full-text articles. One investigator extracted relevant data. A senior reviewer checked data for completeness and accuracy.Data synthesis: We included 104 experimental and observational studies. If data were sufficient, we conducted meta-analyses of randomized controlled trials on the relative risk of specific adverse events. Findings indicate that the spectrum of adverse events is similar. The frequency of specific adverse events, however, differed across drugs. Venlafaxine was associated with a significantly higher rate of nausea and vomiting than selective serotonin reuptake inhibitors. Compared with other drugs, paroxetine frequently led to more sexual adverse effects and bupropion to fewer such effects; mirtazapine and paroxetine was associated with more weight gain and sertraline with a higher rate of diarrhoea. Overall, however, these differences did not lead to different discontinuation rates. The evidence is insufficient to draw conclusions about rare but severe adverse events.Conclusions: Adverse event profiles are similar among second-generation antidepressants. However, different frequencies of specific adverse events might be clinically relevant and influence the choice of a treatment.

P-1102 - Comparative effectiveness of second generation antidepressants in the pharmacologic treatment of adult depression

PURPOSE We wanted to review systematically the efficacy, effectiveness, and safety of inhaled corticosteroids with respect to health outcomes in patients with chronic obstructive pulmonary disease (COPD). METHODS We searched MEDLINE, EMBASE, The Cochrane Library, and the International Pharmaceutical Abstracts to identify relevant articles. We limited evidence to double-blinded randomized controlled trials (RCTs) for efficacy, but we also reviewed observational evidence for safety. Outcomes of interest were overall mortality, exacerbations, quality of life, functional capacity, and respiratory tract symptoms. When possible, we pooled data to estimate summary effects for each outcome. RESULTS Thirteen double-blinded RCTs determined the efficacy of an inhaled corticosteroid compared with placebo; 11 additional studies assessed the safety of inhaled corticosteroid treatment in patients with asthma or COPD. Overall, COPD patients treated with inhaled corticosteroids experienced significantly fewer exacerbations than patients taking placebo (relative risk [RR] = 0.67; 95% CI, 0.59–0.77). No significant difference could be detected for overall mortality (RR = 0.81; 95% CI, 0.60–1.08). Evidence on quality of life, functional capacity, and respiratory tract symptoms is mixed. Adverse events were generally tolerable; pooled discontinuation rates did not differ significantly between inhaled corticosteroid and placebo treatment groups (RR = 0.92; 95% CI, 0.74–1.14). Observational evidence, however, indicates a dose-related risk of cataract and open-angle glaucoma. Severe adverse events, such as osteoporotic fractures, are rare; the clinical importance of the additional risk is questionable. CONCLUSIONS Overall, the risk-benefit ratio appears to favor inhaled corticosteroid treatment in patients with moderate to severe COPD. Existing evidence does not indicate a treatment benefit for patients with mild COPD.

Functional outcomes of drug treatment in Alzheimer's disease: A systematic review and meta-analysis.

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.