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Introduction Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Some have questioned whether these medications are equally effective in older adults. Objectives To compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, venlafaxine, vilazodone, and vortioxetine for the treatment of MDD in older adults and to assess whether efficacy differed in older adults compared with the adults of all ages. Methods To identify relevant studies, we searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and CINAHL through December, 2014. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias. We conducted mixed treatment comparisons to derive indirect estimates of the comparative efficacy among all second-generation antidepressants and we conducted meta-regression by assessing whether efficacy differed in trials that enrolled older adults compared with trials that enrolled adults of any age. The outcome was treatment response as measured by ≥50% improvement from baseline on the HAM-D. Results Evidence on older adults compared with adults of any age is sparse. In older adults, evidence indicates that efficacy does not differ substantially among second-generation antidepressants; however, there may be some differences in adverse events. Our meta-regression found a trend toward lesser efficacy of SGAs in older adults than adults of any age. Conclusions Our findings suggests that SGAs may be less effective in older populations. There is a great need for research focusing directly on the efficacy and safety of SGAs in older adults. [ABSTRACT FROM AUTHOR]

Introduction Seasonal Affective Disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occur during autumn or winter and remit in spring. Second-generation antidepressants (SGAs) are established interventions to treat acute episodes of SAD. However, little is known about the efficacy and potential harms of these interventions for preventing SAD. Objectives To assess the efficacy and safety of SGAs to prevent SAD and improve patient–centered outcomes in adults with a history of SAD. Methods We searched the Cochrane Depression, Anxiety and Neuorosis Review Group's specialised register, EMBASE, MEDLINE, PsycINFO and the Cochrane Central Register of Controlled Trials. In addition, we searched pharmaceutical industry trials registers via the Internet to identify unpublished trial data. We also conducted grey literature searches and handsearches of pertinent reference lists. Two authors reviewed the evidence, abstracted data, and assessed risk of bias. We pooled data for meta-analysis when participant groups were similar and the studies assessed the same treatments with the same comparator. Results We did not find eligible studies for most comparisons. We included three RCTs comparing bupropion XL with placebo. Statistically significantly fewer patients treated with bupropion experienced the onset of a major depressive episode during winter months. The overall risk of adverse events was similar between treatment groups. However, bupropionn-treated patients had significantly higher risk for headache, insomnia, and nausea. Conclusion The evidence base on SGA treatment to prevent SAD is limited. Future studies are needed to provide a sufficient evidence base for clinical decisionmaking. [ABSTRACT FROM AUTHOR]

Introduction: Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Two published CERs provide conflicting evidence about the comparative efficacy and safety of second-generation antidepressants for the treatment of MDD. Objectives: 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 MDD in adults. Methods: We updated a CER published in 2007 by the Agency for Healthcare Research and Quality searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two persons 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: Overall, no substantial differences in efficacy could be detected among second-generation antidepressants. Statistically significant differences in response rates between some compared drugs are small and likely not clinically relevant. 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 caused lower rates of sexual dysfunction than other antidepressants. 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. [ABSTRACT FROM AUTHOR]

Introduction: People with particular medical illnesses are at an increased risk of depression. Similarly, other psychiatric or behavioral illnesses increase the risk of depressive disorders. There is a growing interest in the comparative benefits and harms of second-generation antidepressants for treating depression with co-occurring illness. Objectives: 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 syndromes in certain demographic populations (e.g., older adults) and in subgroups with comorbidities. Methods: We updated a comparative effectiveness review (CER) published in 2007 by the Agency for Healthcare Research and Quality searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias. In addition, investigators graded the strength of the body of evidence. Results: Evidence on subgroups is sparse. Head-to-head RCTs often exclude subgroups. We found no studies designed to compare a particular subgroup with the general population. In older adults, efficacy does not differ substantially among second-generation antidepressants; however, there may be some differences in adverse events. We found no head-to-head trials comparing efficacy and harms in different race or ethnic groups. Comparative evidence on comorbidities was limited to a subgroup analysis of depressed adults with generalized anxiety disorder. Conclusions: There is a great need for research focusing directly on the efficacy and safety of second-generation antidepressants in these more vulnerable populations. [ABSTRACT FROM AUTHOR]

Introduction: Clinicians treating patients with Major Depressive Disorder (MDD) might favor one second-generation antidepressant (SGA) because of perceived benefits for the accompanying symptoms of MDD. Objectives: To compare the efficacy of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of the accompanying symptoms of MDD. Methods: This review is part of a larger review on the comparative effectiveness of SGAs for MDD. We searched MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias. Results: We located 26 head-to-head and 7 placebo-controlled trials that provided evidence for this review. We did not locate any studies on treating accompanying appetite change, low energy, melancholia, or psychomotor change. There was no evidence for many comparisons and we were unable to conduct quantitative analysis for any comparisons. For the comparisons that were studied, we concluded that the SGAs are similarly efficacious for treating anxiety, insomnia, pain, and somatization. The strength of the evidence for these conclusions is low (meaning further research is very likely to have an important impact on our confidence in the estimate of the effect and is likely to change the estimate). Conclusions: Our findings indicate that the existing evidence does not warrant the choice of one second-generation antidepressant over another based on greater efficacy for the accompanying symptoms of depression. [ABSTRACT FROM AUTHOR]

Introduction: Extended-release formulations of antidepressants have been marketed as a strategy to increase patient adherence. Changes in the formulation of drugs, however, could be related to changes in efficacy and tolerability. Among second-generation antidepressants, bupropion, fluoxetine, mirtazapine, paroxetine, and venlafaxine are available in immediate- and extended-release formulations. Objectives: To compare the efficacy, tolerability, and adherence of immediate- versus extended-release formulations of second-generation antidepressants for the treatment of major depressive disorder (MDD) in adults. Aim: To provide an evidence base for clinicians when choosing immediate- or extended-release formulations of antidepressants for the treatment of MDD. Methods: We conducted a comparative effectiveness review for the U.S. Agency for Healthcare Research and Quality searching PubMed, EMBASE, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two people independently reviewed the literature, abstracted data, and rated the risk of bias. Results: Six RCTs and one observational study provided evidence about the comparative efficacy, tolerability, and adherence of bupropion SR (sustained release) versus bupropion XL (extended release), fluoxetine daily vs. fluoxetine weekly, paroxetine IR (immediate release) versus paroxetine CR (continuous release), and venlafaxine IR versus venlafaxine XR (extended release). Overall, no substantial differences in efficacy and safety could be detected. Open-label and observational evidence indicated better adherence for bupropion XL and fluoxetine weekly than for immediate-release medications. No differences in adherence could be detected between paroxetine IR and paroxetine CR. Conclusions: Our findings indicate similar efficacy and tolerability between immediate- and extended-release formulations. Whether extended-release formulations lead to better adherence remains unclear. [ABSTRACT FROM AUTHOR]

Introduction: Since the black box warning of the FDA (Food and Drug Administration) regarding an increased risk of suicidality in children and adolescents treated with antidepressants, cautious prescription of antidepressant drugs in young patients became even more important. In the light of potentially severe side effects the comparative effectiveness and harms of antidepressants should be known to clinicians to provide optimal treatment. Objectives: To compare the benefits and harms of second-generation antidepressants for the treatment of Major Depressive Disorder (MDD) in children and adolescents. Aims: To provide an evidence base for clinicians and policymakers when making informed decisions regarding the prescription of Selective Serotonin Reuptake Inhibitors and other newer antidepressants. Methods: We updated a comparative effectiveness report of the Oregon Drug Effectiveness Review Project searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to August 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias. Results: We could not identify any head-to-head trials. There is insufficient evidence to compare one second-generation antidepressant to another in pediatric outpatients with MDD. Evidence from a systematic review of published and unpublished data indicates, that in children and adolescents only fluoxetine shows a good risk-benefit ratio. Conclusions: To date, the evidence is insufficient to make any clear inferences about the comparative benefits and harms of second-generation antidepressants for the treatment of MDD in children. Clinicians must be aware of the small benefits and the high potential risks when prescribing antidepressant medications to children and adolescents. [ABSTRACT FROM AUTHOR]

Introduction: Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Two published comparative effectiveness reviews (CER) provide conflicting evidence about the comparative efficacy and safety of second-generation antidepressants for treating MDD. Objectives: 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 MDD in adults. Methods: We updated a CER published in 2007 by the Agency for Healthcare Research and Quality searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two persons 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: Overall, no substantial differences in efficacy could be detected among second-generation antidepressants. Statistically significant differences in response rates between some compared drugs are small and likely not clinically relevant. 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 caused lower rates of sexual dysfunction than other antidepressants. 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. [ABSTRACT FROM AUTHOR]

Introduction: Extended-release formulations of antidepressants have been marketed as a strategy to increase patient adherence. Changes in the formulation of drugs, however, could be related to changes in efficacy and tolerability. Among second-generation antidepressants bupropion, fluoxetine, mirtazapine, paroxetine, and venlafaxine are available in immediate- and extended-release formulations. Objectives: To compare the efficacy, tolerability, and adherence of immediate- versus extended-release formulations of second-generation antidepressants for the treatment of major depressive disorder (MDD) in adults. Aim: To provide an evidence base for clinicians when choosing immediate- or extended-release formulations for the treatment of MDD. Methods: We conducted a comparative effectiveness review for the U.S. Agency for Healthcare Research and Quality searching PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts up to January 2011. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias. Results: Six RCTs and one retrospective cohort study provided evidence about the comparative efficacy, tolerability, and adherence of bupropion XL (extended release) versus bupropion SR (sustained release), fluoxetine daily versus fluoxetine weekly, paroxetine IR (immediate release) versus paroxetine CR (continuous release), and venlafaxine IR versus venlafaxine XR (extended release). Overall, no substantial differences in efficacy and safety could be detected. Open-label and observational evidence indicated better adherence for bupropion XL and fluoxetine weekly than for immediate-release medications. No differences in adherence could be detected between paroxetine IR and paroxetine CR. Conclusions: Our findings indicate similar efficacy and tolerability between immediate- and extended-release formulations. Whether extended-release formulations lead to better adherence remains unclear. [ABSTRACT FROM AUTHOR]

Introduction: Patients with depression often suffer from accompanying symptoms that may influence the choice of second-generation antidepressant (SGA) therapy. Objectives: To determine the comparative effectiveness of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for treating common accompanying symptoms of depression. Methods: We searched MEDLINE®, Embase, The Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to August 2011 and identified unpublished research. Two persons independently reviewed abstracts and full-text articles and abstracted data. We included randomized, head-to-head trials of SGAs (>6 weeks, N>40). We graded the strength of the evidence for each symptom as high, moderate, low, or insufficient using the US Agency for Healthcare Research and Quality (AHRQ) approach. Results: We located 22 head-to-head trials for anxiety; insomnia; pain; melancholia; psychomotor change; or somatization. For the majority of symptoms the strength of the evidence was low or insufficient. For treating anxiety and treating depression in patients with accompanying anxiety, moderate evidence suggests there is no difference between SGAs. Likewise, for patients with depression and pain, moderate evidence suggests there is no difference between paroxetine and duloxetine for reducing the pain. Conclusions: Evidence guiding the selection of an SGA based on accompanying symptoms of depression is limited. Very few trials were designed and adequately powered to answer questions about accompanying symptoms; analyses were generally of subgroups in larger depression trials. Where evidence is available, it suggests no difference between SGAs in their efficacy for treating the depressive episode or the accompanying symptom. [ABSTRACT FROM AUTHOR]

Objective: To summarize the best available evidence regarding the short- and long-term health effects of cow's milk intake in healthy, full-term infants up to 3 years of age., Design: We conducted a systematic review and meta-analysis., Setting: We searched MEDLINE (via PubMed), EMBASE and the Cochrane Library between 1960 and July 2013 and manually reviewed reference lists of pertinent articles. Two researchers independently reviewed abstracts and full-text articles and extracted relevant data., Subjects: We included (randomized/non-randomized) controlled trials and observational studies., Results: We included data from twenty-three studies (one randomized controlled trial, four non-randomized controlled trials, eight case-control studies and ten cohort studies) for the evidence synthesis. Pooled results of four studies revealed a higher risk of Fe-deficiency anaemia for infants consuming cow's milk compared with those consuming follow-on formula (relative risk=3·76; 95 % CI 2·73, 5·19). For type 1 diabetes mellitus, six out of seven case-control studies did not show a difference in the risk of developing this disease based on the age of introduction of cow's milk. We did not find negative associations for other health effects., Conclusions: Cow's milk consumption in infancy is associated with an increased risk of developing Fe-deficiency anaemia. Limiting cow's milk consumption may be important to ensure an adequate Fe intake for infants and toddlers. High-quality patient information for caregivers is needed on how infants' Fe requirements can be met.

Background: Uncertainty about the applicability of controlled trial findings is an increasing concern for clinicians and policy decision makers. This study aimed to determine whether information reported in studies included in systematic reviews was adequate enough to assess their applicability., Methods: We used the databases of four recently conducted systematic reviews on the comparative efficacy and safety of second-generation antidepressants, inhaled corticosteroids, Alzheimer's drugs, and targeted immune modulators. We developed and pilot-tested a questionnaire to assess the adequacy of reporting with respect to seven previously validated criteria of study design that distinguish explanatory from pragmatic studies. For each of the 137 included studies, two reviewers independently assessed the adequacy of reporting., Results: Overall, only 12 percent of the included studies provided sufficient information to reliably distinguish explanatory from pragmatic studies. The areas with the greatest lack of reporting were the setting of the study, methods of adverse event assessment, and sample size considerations to determine a minimally important difference from a patient perspective., Conclusions: Substantial shortcomings in reporting exist in aspects of study design important to determine whether a study is applicable to specific populations of interest.